Miniature optical coherence tomography-ultrasound probe for automatically coregistered three-dimensional intracoronary imaging with real-time display.
ABSTRACT: We have developed a novel miniature integrated optical coherence tomography (OCT)-intravascular ultrasound (IVUS) probe, with a 1.5-mm-long rigid part and 0.9-mm outer diameter, for real-time intracoronary imaging of atherosclerotic plaques and guiding of interventional procedures. By placing the OCT ball lens and IVUS transducer back-to-back at the same axial position, this probe can provide automatically coregistered, coaxial OCT-IVUS imaging. To demonstrate its real-time capability, three-dimensional OCT-IVUS imaging of a pig's coronary artery displaying in polar coordinates, as well as images of three major types of atherosclerotic plaques in human cadaver coronary segments, were obtained using this probe and our upgraded system. Histology validation is also presented.
Project description:Acute coronary syndromes (ACS) secondary to coronary vessel plaques represent a major cause of cardiovascular morbidity and mortality worldwide. Advancements in imaging technology over the last 3 decades have continuously enabled the study of coronary plaques via invasive imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The introduction of near-infrared spectroscopy (NIRS) as a modality that could detect the lipid (cholesterol) content of atherosclerotic plaques in the early nineties, opened the potential of studying "vulnerable" or rupture-prone, lipid-rich coronary plaques in ACS patients. Most recently, the ability of NIRS-IVUS to identify patients at risk of future adverse events was shown in a prospective multicenter trial, the Lipid-Rich-plaque Study. Intracoronary NIRS-IVUS imaging offers a unique method of coronary lipid-plaque characterization and could become a valuable clinical diagnostic and treatment monitoring tool.
Project description:Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72?mm-long artery in 4?seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real-time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions.
Project description:Optical coherence tomography (OCT) is a high-resolution imaging technique that is increasingly used for intracoronary imaging to characterize coronary atherosclerotic plaques and vascular responses after coronary stent implantation. Introduction of optical frequency-domain imaging (OFDI; second generation OCT) has simplified practical use of this novel imaging modality resulting in a more widespread availability in interventional cardiology. Here we highlight recent insights into the acute and chronic vascular response after coronary stent implantation by OCT imaging. OCT provides cross-sectional images with approximately 10-fold higher resolution as compared to intravascular-ultrasound (IVUS), allowing for precise evaluation of tissue coverage and malapposition of coronary stent struts. More than 30 studies using OCT to compare vascular responses to different stents have now been reported. Recent studies have examined the relation between OCT-image characteristics and tissue composition around stent struts. OCT is used for evaluation of novel stent concepts, such as bioengineered stents and bioabsorbable stents, where it provides more accurate information than IVUS. While intracoronary OCT imaging is further developed, including faster 3D-OCT-image-reconstruction, larger OCT studies/registries with standardized analysis will provide more insights into clinical implications of observations from OCT-imaging after coronary stent implantation.
Project description:Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.
Project description:BACKGROUND AND AIMS:Significant macrophages infiltration in advanced atherosclerotic plaques promotes acute coronary events. Hence, the clinical imaging of macrophage content in coronary atherosclerotic plaques could potentially aid in identifying patients most at risk of future acute coronary events. The aim of this study was to introduce and validate a simple intravascular optical coherence tomography (IV-OCT) image processing method for automated, accurate and fast detection of macrophage infiltration within coronary atherosclerotic plaques. METHODS:This method calculates the ratio of the normalized-intensity standard deviation (NSD) values estimated over two axially-adjacent regions of interest in an IV-OCT cross-sectional image (B-scan). When applied to entire IV-OCT B-scans, this method highlights plaque areas with high NSD ratio values (NSDRatio), which was demonstrated to be correlated with the degree of coronary plaque macrophage infiltration. RESULTS:Using an optimized NSDRatio threshold value, coronary plaque macrophage infiltration could be detected with ~88% sensitivity and specificity in a database of 28 IV-OCT scans from postmortem coronary segments. For comparison, using an optimized NSD threshold value, considered the standard IV-OCT signature for macrophages, coronary plaque macrophage infiltration could be detected with only ~55% sensitivity and specificity. CONCLUSIONS:The proposed NSDRatio method significantly increases the sensitivity and specificity for the detection of coronary plaque macrophage infiltration compared to the standard NSD method. This computationally efficient method can be seamlessly implemented within standard IV-OCT imaging systems for in-vivo real-time imaging of macrophage content in coronary plaques, which could potentially aid in identifying patients most at risk of future acute coronary events.
Project description:New tomographic cardiovascular imaging tests, such as intravascular ultrasonography (IVUS), coronary computed tomography (CT) angiography and magnetic resonance imaging (MRI), can be used to assess atherosclerotic plaques for the characterization and early staging of coronary artery disease (CAD). Although IVUS images have very high resolution capable of revealing very early preclinical CAD, it is an invasive technique used clinically only in conjunction with a coronary intervention. Multiple-slice coronary CT angiography, which is noninvasive, shows promise as a diagnostic method for CAD. New 64-slice cardiac CT technology has high accuracy for the detection of lesions obstructing more than 50% of the lumen, with sensitivity, specificity, and positive and negative predictive values all better than 90% in patients without known CAD. Cardiac MRI is also improving accuracy in coronary plaque detection and offers a better opportunity for plaque characterization. With further advances in tomographic imaging of coronary atheromas, the goal will be to detect plaques earlier in the development of CAD and to characterize the plaques most likely to generate a clinical event.
Project description:We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.
Project description:Existing clinical intravascular imaging modalities are not capable of accurate detection of critical plaque pathophysiology in the coronary arteries. This study reports the first intravascular catheter combining intravascular ultrasound (IVUS) with multispectral fluorescence lifetime imaging (FLIm) that enables label-free simultaneous assessment of morphological and biochemical features of coronary vessels in vivo. A 3.7 Fr catheter with a fiber-optic channel was constructed based on a 40?MHz clinical IVUS catheter. The ability to safely acquire co-registered FLIm-IVUS data in vivo using Dextran40 solution flushing was demonstrated in swine coronary arteries. FLIm parameters from the arterial wall were consistent with the emission of fluorophores present in healthy arterial wall (collagen, elastin). Additionally, structural and biochemical features from atherosclerotic lesions were acquired in ex vivo human coronary samples and corroborated with histological findings. Current results show that FLIm parameters linked to the amount of structural proteins (e.g. collagen, elastin) and lipids (e.g. foam cells, extracellular lipids) in the first 200??m of the intima provide important biochemical information that can supplement IVUS data for a comprehensive assessment of plaques pathophysiology. The unique FLIm-IVUS system evaluated here has the potential to provide a comprehensive insight into atherosclerotic lesion formation, diagnostics and response to therapy.
Project description:For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. Ex vivo and in vivo experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality.
Project description:AIMS:Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability. METHODS AND RESULTS:We prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65-0.78 vs. 0.59, CI: 0.57-0.62; P?<?0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72-0.88 vs. 0.66, CI: 0.58-0.73; P?<?0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82-0.91 vs. 0.65, CI: 0.64-0.66; P?<?0.001). CONCLUSION:Coronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.