Author + information
- Received August 6, 2015
- Revision received October 8, 2015
- Accepted November 3, 2015
- Published online November 1, 2016.
- Giovanni J. Ughi, PhDa,
- Hao Wang, PhDa,
- Edouard Gerbaud, MDa,
- Joseph A. Gardecki, PhDa,
- Ali M. Fard, PhDa,
- Ehsan Hamidi, PhDa,
- Paulino Vacas-Jacques, PhDa,
- Mireille Rosenberg, PhDa,
- Farouc A. Jaffer, MD, PhDa,b,∗∗ ( and )
- Guillermo J. Tearney, MD, PhDa,c,d,∗ ()
- aWellman Center for Photomedicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
- bCardiovascular Research Center and Cardiology Division, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts
- cDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- dHarvard-MIT Health Sciences and Technology, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Guillermo J. Tearney, Massachusetts General Hospital, Wellman Center for Photomedicine, 40 Blossom Street, BHX-604A, Boston, Massachusetts 02114.
- ↵∗∗Dr. Farouc Jaffer, Massachusetts General Hospital, Cardiovascular Research Center, Simches Research Building, Room 3206, 55 Fruit Street, Boston, Massachusetts 02114.
Objectives The authors present the clinical imaging of human coronary arteries in vivo using a multimodality optical coherence tomography (OCT) and near-infrared autofluorescence (NIRAF) intravascular imaging system and catheter.
Background Although intravascular OCT is capable of providing microstructural images of coronary atherosclerotic lesions, it is limited in its capability to ascertain the compositional/molecular features of plaque. A recent study in cadaver coronary plaque showed that endogenous NIRAF is elevated in necrotic core lesions. The combination of these 2 technologies in 1 device may therefore provide synergistic data to aid in the diagnosis of coronary pathology in vivo.
Methods We developed a dual-modality intravascular imaging system and 2.6-F catheter that can simultaneously acquire OCT and NIRAF data from the same location on the artery wall. This technology was used to obtain volumetric OCT-NIRAF images from 12 patients with coronary artery disease undergoing percutaneous coronary intervention. Images were acquired during a brief, nonocclusive 3- to 4-ml/s contrast purge at a speed of 100 frames/s and a pullback rate of 20 or 40 mm/s. OCT-NIRAF data were analyzed to determine the distribution of the NIRAF signal with respect to OCT-delineated plaque morphological features.
Results High-quality intracoronary OCT and NIRAF image data (>50-mm pullback length) were successfully acquired without complication in all patients (17 coronary arteries). The maximum NIRAF signal intensity of each plaque was compared with OCT-defined type, showing a statistically significant difference between plaque types (1-way analysis of variance, p < 0.0001). Interestingly, coronary arterial NIRAF intensity was elevated only focally in plaques with a high-risk morphological phenotype (p < 0.05), including OCT fibroatheroma, plaque rupture, and fibroatheroma associated with in-stent restenosis.
Conclusions This OCT-NIRAF study demonstrates that dual-modality microstructural and fluorescence intracoronary imaging can be safely and effectively conducted in human patients. Our findings show that NIRAF is associated with a high-risk morphological plaque phenotype. The focal distribution of NIRAF in these lesions furthermore suggests that this endogenous imaging biomarker may provide complementary information to that obtained by structural imaging alone.
Intravascular optical coherence tomography (OCT) is a high-resolution imaging technique that is increasingly being used in interventional cardiology for the investigation and management of coronary artery disease (1,2). OCT enables the visualization of the artery wall microstructure, including morphological features related to coronary events such as lipid-containing regions, macrophage accumulations, thin-cap fibroatheromas (TCFAs), erosions and ruptures, and thrombi and calcified nodules (1,2). Owing to its capability to enable a clear view of the detailed arterial morphology and implanted arterial stents, OCT has also been used to assess the response of the artery wall after percutaneous coronary intervention (PCI) (1,2).
Even though OCT provides an unprecedented level of morphological detail, it does have limitations that constrain its diagnostic capabilities. Key plaque features such as lipid, for example, manifest as low OCT signal. The use of negative contrast features can confound diagnosis because signal loss may arise from a variety of different sources such as macrophage shadowing, intraluminal debris, and image artifacts (3,4). Furthermore, the capability of OCT to differentiate non-necrotic intracellular and extracellular lipid accumulations from necrotic core lipid has never been shown and therefore remains an unanswered question in the field (2,4). This ambiguity is problematic because studies have shown that a definitive diagnosis of necrosis is needed to distinguish rupture-prone lesions (5). In addition, microstructure alone does not provide a complete understanding of coronary artery disease, as the underlying mechanisms of coronary plaque development that lead to disruption and acute thrombosis are multifactorial, involving a complex interaction between structural, compositional, and biomechanical characteristics and cellular and molecular processes in the vessel wall (5).
Fluorescence molecular imaging has been proposed to complement OCT for studying plaque pathobiological mechanisms (6,7). Intravascular near-infrared fluorescence using targeted molecular agents has been shown to elucidate inflammatory activity and fibrin accumulation in mice (8) and rabbit (7,9) arteries, but these agents are not yet approved for human use. Detection of fluorescence from naturally occurring molecules, also known as autofluorescence, is closer to clinical application because it can be detected without the administration of exogenous agents. Autofluorescence excited in the ultraviolet and the visible portions of the electromagnetic spectrum has been studied in human plaques ex vivo where the signal relates to elastin, collagen, and nicotinamide adenine dinucleotide (10,11). Recently, red-excited (633-nm) near-infrared autofluorescence (NIRAF), with emission detected between 700 and 900 nm, has been shown in cadaver coronary arteries to be specifically elevated in advanced necrotic core–containing lesions (12), including thin-cap fibroatheroma (TCFA), the most common type of plaque implicated in acute coronary syndromes and acute myocardial infarction.
Based on the potential of the OCT and NIRAF combination to improve our detection of necrotic core lesions and specifically TCFAs, we developed a human-use OCT-NIRAF system and catheter. Here we describe a first-in-human safety and feasibility study of this multimodality intravascular imaging technology in patients and report our findings regarding the spatial distribution of the NIRAF signal with respect to colocalized OCT images of tissue microstructure in vivo.
Patients undergoing PCI at Massachusetts General Hospital (Boston, Massachusetts) were enrolled between July 2014 and January 2015. All patients provided informed consent, and the study was approved by the Massachusetts General Hospital (Partners Healthcare) institutional review board.
Dual-modality OCT-NIRAF imaging system
We created a dedicated, dual-modality OCT-NIRAF system that implements state-of-the-art OCT (1,250 to 1,370 nm) and NIRAF, excited at 633 nm and detected between 675 and 950 nm (Online Figure 1). This system acquires synchronized OCT and NIRAF data at a rate of 100 frames/s. The OCT-NIRAF coronary imaging procedure is identical to that of current intravascular OCT, in which volumetric (3-dimensional) OCT-NIRAF data are obtained by rotating and translating the driveshaft at a constant speed, producing a helical scan.
Clinical intracoronary OCT-NIRAF imaging
As in routine clinical intravascular OCT imaging (1,2), the dual-modality catheter was advanced over a 0.014-inch guidewire and through a 6-F guide catheter placed in a coronary ostium. The OCT-NIRAF catheter was advanced distal to a lesion of interest, and images were acquired during a manual contrast injection at a rate of ∼3 to 4 ml/s for ∼3 s. The driveshaft was retracted at a pullback speed of either 20 or 40 mm/s. OCT-NIRAF imaging of the vessel undergoing PCI was performed in all cases, and additional major coronary vessels were imaged as time permitted.
NIRAF emission intensity data were processed by first subtracting the image background. We then automatically calibrated NIRAF emission intensities based on the distance between the catheter and the artery wall as determined by OCT, so that the fluorescence signal could be quantitatively compared among patients (6,13). Quantitative NIRAF data were normalized between 0 and 1 using the minimum and maximum NIRAF values acquired in the study. NIRAF data were displayed using a linear color look-up table (dark blue [low NIRAF] to white [high NIRAF]). OCT and NIRAF data were fused with the calibrated, normalized, and color-mapped NIRAF data, presented as an annulus around the gray-scale OCT image, in a manner similar to that used for near-infrared spectroscopy (NIRS) IVUS (14). En face 2-dimensional NIRAF maps were also generated, similar in format to that of a NIRS chemogram, with the catheter’s scan angle on the vertical axis and the pullback distance on the horizontal axis. OCT images were displayed using a logarithmic gray-scale look-up table (15).
Three-dimensional reconstructions of OCT-NIRAF data were obtained after frame-to-frame semiautomatic registration to correct for artifacts generated by cardiac motion and mechanical scanning catheter–based acquisition. Plaques were manually segmented, and different colors were assigned as follows: artery wall, gray; calcified plaques, white; and lipid-rich plaque, yellow. In addition, stent struts were automatically segmented (16,17) and rendered in red. Processed OCT-NIRAF images were imported into volume-rendering software (OsiriX 6.5.2, The OsiriX Foundation, Geneva, Switzerland), and 3-dimensional data were visualized as volumes (perspective volume rendering) with semitransparent opacity tables (15). The NIRAF signal was rendered over the artery wall with semitransparent opacity levels, tuned for optimal visualization.
In order to correlate the NIRAF emission intensities with the different plaque features, lesions were manually segmented using standard OCT image interpretation criteria (1,2). Tissue type was categorized as normal vessel wall, fibrotic, fibrocalcific, thick-cap fibroatheroma (ThCFA) if cap thickness was >65 μm, TCFA if cap thickness was ≤65 μm, and plaque rupture. The plaques were selected by an expert OCT image reader (G.J.U.) blinded to NIRAF data to avoid bias. Each plaque included multiple adjacent OCT-NIRAF frames. The maximum normalized NIRAF signal intensity was calculated using all A-scan lines within the plaque. Plaques with a maximum normalized NIRAF intensity >0.4 were arbitrarily classified as having a high NIRAF signal, moderate NIRAF plaques had a maximum normalized signal between 0.2 and 0.4, low NIRAF lesions had a maximum normalized signal between 0.05 and 0.2, and plaques negative for NIRAF were those with a maximum normalized NIRAF signal <0.05. Macrophage accumulations within fibroatheroma caps were quantified using the normalized SD (NSD) parameter (18). NSD values >7 (median value of the NSD range) were considered to be elevated in this study. This analysis was performed on each OCT fibroatheroma frame showing moderate or high NIRAF and on an equally numbered, randomly selected set of atheroma frames showing low or absent NIRAF. Frames showing OCT image artifacts (e.g., nonuniform rotational distortion, seamline artifact, or blood in the lumen) were excluded from all analyses. NIRAF signal reproducibility among repeated pullbacks from the same coronary segment was assessed by first registering 2 datasets using anatomic landmarks and known pullback speeds. A 1-dimensional pullback plot was then generated for each NIRAF dataset by taking the maximum NIRAF signal for each frame for each pullback position. Reproducibility was quantified using Pearson’s correlation coefficient computed from paired, 1-dimensional NIRAF pullback datasets.
In order to quantify our observations that NIRAF is only elevated focally in OCT-delineated atherosclerotic plaques, we measured the fibroatheroma arc distribution in degrees as determined by OCT using the lumen’s centroid as the origin and repeated the same procedure for NIRAF. These measurements were made for all of the plaques imaged in this study that exhibited moderate or high NIRAF emission intensity. The same procedure was used to compare NIRAF and macrophage density (NSD) angular distributions.
The statistical analysis reported in this study was performed using Matlab version 8.4.0 (MathWorks, Natick, Massachusetts) and Matlab Statistics Toolbox version 9.1. One-way analysis of variance and pairwise Kruskal-Wallis analysis (with the Mann-Whitney U test and without adjustment for multiple comparisons) were used to compare maximum normalized NIRAF between OCT-defined plaque type. No corrections for multiple observations within subjects or vessels were applied. Continuous data are expressed as mean ± SD or median (interquartile range) when appropriate, and p values <0.05 are considered statistically significant.
At total of 12 patients were imaged using the OCT-NIRAF catheter. Table 1 depicts baseline characteristics of the enrolled patients. A total of 17 major coronary arteries were imaged simultaneously using colocalized OCT and NIRAF, encompassing 33 OCT-NIRAF pullbacks. Good-quality OCT-NIRAF datasets (average length: 52 ± 10 mm) were obtained for each patient. The mean number of pullbacks per patient was 2.75 ± 1.23, and the average amount of contrast administered to each patient was 44 ± 26 ml, with a mean of 14 ± 2 ml per OCT-NIRAF pullback. In a substudy of 4 repeated pullbacks, NIRAF reproducibility was excellent, with an average Pearson correlation coefficient of 0.925 ± 0.015 (Online Figure 2). There were no patient complications related to the OCT-NIRAF imaging procedure.
Description of representative clinical cases
Figure 1 shows an example of an OCT-NIRAF pullback from the right coronary artery of a 67-year-old male patient who presented with in-stent restenosis of the mid-right coronary artery. This pullback was acquired adjacent to the stented region located in the distal right coronary artery, along a nonstenotic segment (Figure 1A). OCT imaging revealed a long segment of normal coronary wall and intimal hyperplasia with concomitant minimal NIRAF signal throughout (Figures 1B and 1D). A small calcific lesion located in the middle of the pullback was NIRAF negative (Figure 1C).
Strong NIRAF was only seen in regions of plaque with high-risk structural features (e.g., lipid-containing plaques, thin-fibrous caps, and/or rupture with thrombus), as determined by OCT. Online Figure 3 shows an example of an OCT-NIRAF pullback acquired from the left anterior descending coronary artery (LAD) of a diabetic 59-year-old male patient presenting with left circumflex coronary artery (LCx) in-stent restenosis. The angiogram demonstrated diffuse atherosclerotic disease in the LAD. OCT imaging revealed multiple lesions in the LAD, including several fibrocalcific and lipid-rich plaques (Online Figures 3C to 3G). A single focal spot of elevated NIRAF signal was observed in the 2-dimensional NIRAF map (Online Figure 3B). The OCT image at this site in the mid-LAD indicated the presence of a TCFA with an intact cap. Interestingly, the NIRAF signal was only elevated focally in this OCT-TCFA; in the cross section displayed in Online Figure 3F, high NIRAF was located at the 9 o’clock position, whereas the thin cap extended over a much larger arc, from the 7 to 2 o’clock position. All other plaques in this artery were OCT-delineated as fibrotic (Online Figure 3C), fibrocalcific (Online Figure 3E), or ThCFA (Online Figure 3D) and exhibited negligible or low NIRAF signal.
High NIRAF was also found in arterial sites that contained OCT evidence of plaque disruption/erosion and overlying thrombus. Figure 2 shows an example of a TCFA rupture located in the LAD of a 66-year-old diabetic patient presenting with significant stenosis of the proximal LCx (treated artery) and moderate stenosis of the proximal LAD. OCT imaging of the ostial LAD revealed a TCFA with cap rupture (Figures 2C to 2H), including a platelet-rich thrombus overlying the site of cap disruption (Figures 2D and 2G). NIRAF was elevated focally within the OCT-TCFA at the rupture site (Figures 2E and 2H) and at an adjacent location that contained a cholesterol crystal (Figures 2C and 2F). In this pullback, OCT revealed several other lipid-containing plaques (Figure 2I) that were all negative for NIRAF.
The OCT-NIRAF catheter was also used to image early in-stent restenosis (86 days after bare metal stent implantation) in the LCx of the diabetic patient described previously. Because of severe restenosis (70%), OCT-NIRAF was conducted after balloon pre-dilation. In the proximal and middle region of the stented segment, OCT imaging revealed that a portion of the stent was deployed overlying a large fibroatheroma (Figure 3). An elevated NIRAF signal was observed in this area (Figures 3B and 3C). The remaining in-stent restenotic tissue had an OCT appearance of neointimal hyperplasia and exhibited minimal NIRAF signal (Figure 3E).
OCT-NIRAF quantitative analysis
Patient imaging findings revealed NIRAF emission intensity patterns that were distinct from structural or compositional patterns seen with other intravascular coronary imaging modalities (e.g., OCT, IVUS, NIRS) in vivo. From the 17 coronary arteries imaged in this study, a high focal NIRAF signal was found in 5 arteries (29%), a low to moderate NIRAF signal was found in 4 arteries (24%), whereas all the other arteries (n = 8, 47%) were NIRAF negative. After analysis of each pullback, a total of 79 distinct plaques were identified as described in the Methods section. The maximum NIRAF signal intensity of each plaque was compared with the OCT-defined type (Figure 4). There was a statistically significant difference of maximum NIRAF signal between plaque types (1-way analysis of variance, p < 0.0001). OCT-delineated TCFA and plaque rupture cases demonstrated much higher maximum NIRAF signal than all other plaques (p < 0.05). All other groups were statistically different from each other (p < 0.05), with the exception of fibrocalcific plaques and ThCFA (p = 0.65). Although there were only 2 plaque ruptures identified in this cohort, the maximum NIRAF signal for rupture sites was nonsignificantly higher than that of unruptured TCFAs (p = 0.07) (Figure 4).
By comparing OCT and NIRAF lipid arcs, we observed that NIRAF contiguously spanned 23.2 ± 13.0% of the total arc of lipid in OCT fibroatheromas. These findings indicate that in all areas where NIRAF was elevated, it only peaked at specific discrete loci.
OCT macrophage accumulation analysis (92 OCT fibroatheroma frames analyzed) demonstrated that NIRAF is focally associated with OCT measurement of macrophage-rich inflammation, as estimated by the NSD parameter (18). When NIRAF was high, it was always found in areas of elevated NSD (Online Figure 4), but not all areas of high NSD exhibited high NIRAF. Furthermore, NIRAF was only elevated discretely in regions of elevated NSD as NIRAF covered 39.2 ± 12.5% of the elevated NSD arc.
In this paper, we present a first-in-human investigation of multimodality intracoronary OCT and NIRAF imaging in vivo. Our results show that OCT-NIRAF uncovers a unique autofluorescence signature of human coronary atherosclerosis in vivo. The intracoronary NIRAF-OCT procedure was safe and was used in patients similarly as conventional intravascular OCT. Importantly, coregistration and distance correction of OCT and NIRAF data were inherently automatic and facilitated image interpretation. Data acquisition was reliable, and NIRAF was found to be reproducible among multiple pullbacks.
By investigating the spatial relationship between NIRAF and arterial morphological features in vivo, we found that elevated NIRAF was associated with morphological and/or mechanistic features that have been associated with high plaque risk. NIRAF was negative or low in plaques with a low-risk microstructural phenotype as determined by OCT (intimal hyperplasia, fibrous plaque, and fibrocalcific plaque). In contrast, NIRAF was high focally in certain OCT-delineated fibroatheromas and highest in OCT-delineated TCFAs, regions of cap disruption, and areas of fibroatheromas associated with in-stent restenosis. Results of this study also associate elevated NIRAF with indicators of inflammation. NIRAF was found to be only elevated in plaque regions that showed OCT evidence of macrophage accumulations. In combination with our previous ex vivo study (12), these findings support our original rationale for combining OCT and NIRAF to better delineate and characterize atherosclerotic lesions that are at risk of progression. Although the correlation shown here between NIRAF and plaque inflammation has been established using an objective method for OCT image quantification (18,19), these results should be considered hypothesis generating. Plaque components other than macrophages give rise to an appearance of punctate high OCT signal regions, and OCT has not been demonstrated to distinguish between active and inactive macrophages and other macrophage subtypes (20).
The focal spatial distribution of the NIRAF signal was a major unexpected finding of this study that supports the potential additive nature of this imaging biomarker. Elevated NIRAF signal occurred only at discrete locations and, for example, did not subtend the entire fibroatheroma or the entire arc of thin fibrous caps. In addition, NIRAF was only high focally in regions with OCT evidence of high macrophage accumulations; however, the converse was not true in that there were many elevated NSD areas that were NIRAF negative. The observation that NIRAF is only focally elevated in plaques with macrophage accumulations is consistent with the concept of multiple macrophage phenotypes in atherosclerotic lesions.
Additional studies are needed to uncover the specific molecular/chemical mechanisms that produce NIRAF in atherosclerotic plaque to fully understand the biological and clinical relevance of this signal. On the basis of the findings of this study and information gleaned from the published data (21,22), various hypotheses can be made about the potential sources of NIRAF in atherosclerotic plaques and its potential relationship to coronary wall inflammation. NIRAF in atherosclerotic plaque may arise from the modification of lipids and lipoproteins by oxidative stress (21,22). Studies have shown that ceroid, a protein-lipid oxidation byproduct found in atherosclerotic plaque, has a yellow fluorescence spectrum (22), and it is possible that the tail of ceroid’s fluorescence emission may extend into the near infrared. Oxidative stress caused by inflammatory activity may also cross-link surrounding proteins, creating dimers such as dityrosine that are fluorescent in the near infrared (21). Other reports on cancerous tissues (23) have observed tissue autofluorescence, suggesting that it could arise from endogenous porphyrins. Extrapolating to atherosclerosis, it is possible that intraplaque hemorrhage that contributes to lesion development and destabilization may give rise to porphyrins that could in part explain the NIRAF signal observed here.
Although the focal appearance of the NIRAF signal could be due to high biological/spatial specificity of the molecular/chemical entity generating the fluorescence, it also could in part be influenced by the spatial locations of the fluorophores and NIRAF light propagation, given the surrounding tissue’s optical properties. To better characterize the autofluorescence signal detected in vivo, OCT-NIRAF instrumentation can be augmented by detecting the emitted light using a spectrometer rather than a single integrating detector. Use of a spectrometer will allow analysis of the spectral content of the NIRAF emission signal, which may help to determine its molecular/chemical origins. Furthermore, spectral detection can potentially be used to correct for variations of NIRAF signal intensity that are due to the location of the fluorophores in the artery wall and the propagation of NIRAF light through plaque, which may have heterogeneous optical properties.
In this study, we imaged a limited number of patients with relatively low-risk clinical presentations (Canadian Classification System Class II and Class III angina pectoris). Intravascular OCT-NIRAF imaging studies in larger cohorts that include acute coronary syndrome and ST-segment elevation myocardial infarction patients will be required to confirm and expand our findings. Although our data allow a preliminary assessment of the associations between the NIRAF signal and plaque morphology and microstructure, the small size of this study and our inability to acquire specimens for advanced tissue analysis prevent us from making definitive conclusions about the biological or molecular nature of the NIRAF signal. Although these results demonstrate the potential for this NIRAF plaque signature to refine the identification of high-risk plaques in vivo, the applicability of these new lesion characteristics to clinical screening and coronary event prediction remain to be demonstrated as well as the accuracy in assigning an increased risk to plaques with high NIRAF.
With intracoronary OCT-NIRAF, we have demonstrated that a unique human coronary autofluorescence signature can be detected in coronary artery disease patients in vivo. The multimodal OCT-NIRAF structural and fluorescence intracoronary imaging can be conducted in patients with similar ease and safety as that of conventional, standalone intravascular OCT. Findings show that NIRAF is focally elevated in plaque locations where most high-risk morphologic phenotypes are evident. Future investigations will elucidate the specific molecular nature of the NIRAF signal and its pathobiological and clinical relevance. In addition to NIRAF, this work paves the way for demonstrating intravascular OCT and targeted molecular fluorescence in human patients. Such multimodality technologies that combine microstructural and fluorescence imaging will perhaps further expand our armamentarium of tools for coronary plaque diagnosis, improving our capacity to predict plaque progression and refine patient and lesion-specific risk.
COMPETENCY IN MEDICAL KNOWLEDGE: A first-in-human study with a multimodality OCT and NIRAF imaging system and 2.6-F coronary catheter has been conducted. Results showed that co-localized and simultaneously acquired OCT and NIRAF pullback datasets could be safely obtained in human coronary arteries in vivo in a few seconds during a brief, non-occlusive contrast injection. Elevated NIRAF signal was found to be focally associated with a high-risk morphological phenotype, as determined by OCT.
TRANSLATIONAL OUTLOOK: Our results suggest a potential role for intravascular OCT-NIRAF in improving our capability to detect high-risk plaques. Additional studies are required to confirm these initial findings and to determine the molecular/chemical sources of NIRAF in human coronary atherosclerosis.
The authors thank Dr. Amna Soomro and Dr. Aubrey Tiernan (Tearney Lab clinical regulatory team) and Luke Stone (clinical research coordinator at the Cardiology Division of Massachusetts General Hospital) for their help with patient enrollment. The authors also acknowledge Daryl Hyun and Robert Carruth (Tearney Lab engineering team) for their assistance with system and catheter manufacturing; Martin Seifert, Dr. Kanishka Tankala, Dr. George Oulundsen, and Harish Govindarajan (NUFERN, East Granby, Connecticut) for their help in developing and manufacturing the optical fiber used in this study; and Terumo Medical Corporation (Tokyo, Japan) for providing catheter material supplies.
For supplemental figures, please see the online version of this article.
Massachusetts General Hospital has a patent licensing arrangement with Terumo and Canon Corporations. Dr. Tearney (Terumo, Canon), Dr. Gardecki (Canon), and Dr. Jaffer (Canon) have the right to receive royalties as part of these licensing arrangements. The authors have received financial support from Canon USA (support of new technology advancement in OCT-NIRAF), NIH grant R01HL093717 (to Dr. Tearney for the development of the imaging system and imaging of the first 2 patients), NIH grant R01HL HL122388 (to Dr. Jaffer), AHA Grant-in-Aid 13GRNT1760040 (to Dr. Jaffer), and Bullock-Wellman Fellowship Award, Harvard Medical School (to Dr. Ughi). Dr. Jaffer has received research grants from Merck, Kowa, and Siemens; served as a consultant for Abbott Vascular and Boston Scientific; and has received nonfinancial support from Boston Scientific. Dr. Tearney has received royalties from MIT; has received sponsored research from Canon; and has received catheter components from Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Jaffer and Tearney are joint senior authors.
- Abbreviations and Acronyms
- double-clad fiber
- left anterior descending coronary artery
- left circumflex coronary artery
- near-infrared autofluorescence
- near-infrared spectroscopy
- normalized SD
- optical coherence tomography
- percutaneous coronary intervention
- thin-cap fibroatheroma
- thick-cap fibroatheroma
- Received August 6, 2015.
- Revision received October 8, 2015.
- Accepted November 3, 2015.
- American College of Cardiology Foundation
- Bezerra H.G.,
- Costa M.A.,
- Guagliumi G.,
- Rollins A.M.,
- Simon D.I.
- Tearney G.J.,
- Regar E.,
- Akasaka T.,
- et al.
- van Soest G.,
- Regar E.,
- Goderie T.P.,
- et al.
- Imanaka T.,
- Hao H.,
- Fujii K.,
- et al.
- Finn A.V.,
- Nakano M.,
- Narula J.,
- Kolodgie F.D.,
- Virmani R.
- Vinegoni C.,
- Botnaru I.,
- Aikawa E.,
- et al.
- Hara T.,
- Bhayana B.,
- Thompson B.,
- et al.
- Lee S.,
- Lee M.W.,
- Cho H.S.,
- et al.
- Marcu L.,
- Fishbein M.C.,
- Maarek J.M.,
- Grundfest W.S.
- Ughi G.J.,
- Verjans J.,
- Fard A.M.,
- et al.
- Tearney G.J.,
- Waxman S.,
- Shishkov M.,
- et al.
- Ughi G.J.,
- Van Dyck C.J.,
- Adriaenssens T.,
- et al.
- MacNeill B.D.,
- Jang I.K.,
- Bouma B.E.,
- et al.
- Di Vito L.,
- Agozzino M.,
- Marco V.,
- et al.
- Phipps J.E.,
- Vela D.,
- Hoyt T.,
- et al.
- Haka A.S.,
- Kramer J.R.,
- Dasari R.R.,
- Fitzmaurice M.