Showing papers by "Brett E. Bouma published in 2010"

Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging.

Abstract: Optical coherence tomography OCT is rap- idly becoming the method of choice for assessing arterial wall pathology in vivo. Atherosclerotic plaques can be di- agnosed with high accuracy, including measurement of the thickness of fibrous caps, enabling an assessment of the risk of rupture. While the OCT image presents mor- phological information in highly resolved detail, it relies on interpretation of the images by trained readers for the identification of vessel wall components and tissue type. We present a framework to enable systematic and auto- matic classification of atherosclerotic plaque constituents, based on the optical attenuation coefficient t of the tis- sue. OCT images of 65 coronary artery segments in vitro, obtained from 14 vessels harvested at autopsy, are ana- lyzed and correlated with histology. Vessel wall compo- nents can be distinguished based on their optical proper- ties: necrotic core and macrophage infiltration exhibit strong attenuation, t10 mm 1 , while calcific and fi- brous tissue have a lower t25mm 1 . The algorithm is successfully applied to OCT patient data, demonstrating that the analysis can be used in a clinical setting and assist diagnostics of vessel wall pathology. © 2010 Society of Photo-

Atherosclerotic tissue characterization in vivo by optical coherence tomography attenuation imaging

Abstract: Optical coherence tomography OCT is rap- idly becoming the method of choice for assessing arterial wall pathology in vivo. Atherosclerotic plaques can be di- agnosed with high accuracy, including measurement of the thickness of fibrous caps, enabling an assessment of the risk of rupture. While the OCT image presents mor- phological information in highly resolved detail, it relies on interpretation of the images by trained readers for the identification of vessel wall components and tissue type. We present a framework to enable systematic and auto- matic classification of atherosclerotic plaque constituents, based on the optical attenuation coefficient t of the tis- sue. OCT images of 65 coronary artery segments in vitro, obtained from 14 vessels harvested at autopsy, are ana- lyzed and correlated with histology. Vessel wall compo- nents can be distinguished based on their optical proper- ties: necrotic core and macrophage infiltration exhibit strong attenuation, t10 mm 1 , while calcific and fi- brous tissue have a lower t25mm 1 . The algorithm is successfully applied to OCT patient data, demonstrating that the analysis can be used in a clinical setting and assist diagnostics of vessel wall pathology. © 2010 Society of Photo-

>400 kHz repetition rate wavelength-swept laser and application to high-speed optical frequency domain imaging.

Abstract: We demonstrate a high-speed wavelength-swept laser with a tuning range of 104nm (1228-1332nm) and a repetition rate of 403kHz. The design of the laser utilizes a high-finesse polygon-based wavelength-scanning filter and a short-length unidirectional ring resonator. Optical frequency domain imaging of the human skin in vivo is presented using this laser, and the system shows sensitivity of higher than 98dB with single-side ranging depth of 1.7mm over 4dB sensitivity roll-off.

Second-generation optical coherence tomography in clinical practice. High-speed data acquisition is highly reproducible in patients undergoing percutaneous coronary intervention.

Abstract: Introduction and objectives The development of second-generation optical coherence tomography (i.e. Fourier domain optical coherence tomography, FD-OCT) has made it possible to perform high speed pull-backs during image acquisition without the need for transient occlusion of the coronary artery. The objective of this study was to assess the reproducibility of FD-OCT systems for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention. Methods The study included 45 patients scheduled for percutaneous coronary intervention who were enrolled between May and December 2008. Image acquisition was performed by FD-OCT using a non-occlusive technique and employing pull-back speeds ranging from 5 to 20 mm/s. Interstudy, interobserver and intraobserver reproducibility of plaque characterization and stent analysis were assessed. Results Fourier domain imaging was successfully performed in all patients (n=45). The average flush rate was 3±0.4 mL/s and the contrast volume per pull-back was 16.1±3.5 mL. The mean pull-back duration and length were 3.2±1.2 s and 53.3±12.4 mm, respectively. The interstudy reproducibility for visualizing edge dissection, tissue prolapse, intrastent dissection and malapposition was excellent (κ=1). The kappa values for interstudy, interobserver and intraobserver agreement on plaque characterization were 0.92, 0.82 and 0.95, respectively. Conclusions A second-generation OCT system (i.e. FD-OCT) involving high-speed data acquisition demonstrated good interstudy, interobserver and intraobserver reproducibility for characterizing plaque and evaluating stent implantation in patients undergoing a percutaneous coronary intervention.

Challenges on the frontier of intracoronary imaging: atherosclerotic plaque macrophage measurement by optical coherence tomography

Abstract: Cellularity of the fibrous caps of coronary atheromas, manifested by the infiltration of macrophages (average size, 20 to 30 microm), is thought to weaken the structural integrity of the cap and predispose plaques to rupture. Therefore, an imaging technology capable of identifying macrophages within fibroatheroma caps in patients could provide valuable information for assessing plaque rupture risk. Recently, intravascular optical coherence tomography (OCT), a high-resolution coronary imaging modality, with an axial resolution of approximately 10 microm, has been introduced into the clinical setting. OCT images of the microstructure of the coronary artery wall enable accurate plaque-type characterization, supported by histopathological comparison data. Because of its high resolution, OCT may also be used to identify macrophages in vivo. In this paper we review recent developments in OCT for measuring macrophages in atherosclerotic plaques.

Tomografía de coherencia óptica de segunda generación en la práctica clínica. La adquisición de datos de alta velocidad muestra una reproducibilidad excelente en pacientes tratados con intervenciones coronarias percutáneas

Abstract: Introduccion y objetivos Se ha desarrollado una segunda generacion de sistemas de tomografia de coherencia optica (OCT) (dominio de Fourier, OCT-DF) que permiten las retiradas a alta velocidad sin necesidad de ocluir transitoriamente la arteria coronaria durante la obtencion de imagenes. El objetivo de este estudio es evaluar la reproducibilidad de los sistemas de OCT-DF para la caracterizacion de la placa y la evaluacion de la implantacion del stent en pacientes a los que se practican intervenciones coronarias percutaneas. Metodos Entre mayo y diciembre de 2008, se incluyo en el estudio a 45 pacientes para los que se habia programado una intervencion coronaria percutanea. La adquisicion de la OCT-DF se realizo con una tecnica no oclusiva con velocidades de retirada de entre 5 y 20 mm/s. Se evaluo la reproducibilidad entre estudios, entre observadores y en el observador para la caracterizacion de la placa y el analisis de los stents. Resultados La obtencion de imagenes de dominio de Fourier se realizo satisfactoriamente en todos los pacientes (n = 45). El ritmo de infusion medio fue de 3 ± 0,4 ml/s y el volumen de contraste por retirada, 16,1 ± 3,5 ml. La media de duracion y longitud de la retirada fue de 3,2 ± 1,2 s y 53,3 ± 12,4 mm. La reproducibilidad entre estudios, en cuanto a la visualizacion de la diseccion del borde, el prolapso tisular, la diseccion en el stent y la mala aposicion, fue excelente (κ = 1). Los valores de kappa para la coincidencia entre estudios, entre observadores y en el observador en la caracterizacion de la placa fueron 0,92, 0,82 y 0,95 respectivamente. Conclusiones La tecnologia de OCT de segunda generacion, que obtiene datos a alta velocidad, muestra buena reproducibilidad entre estudios, entre observadores y en el observador para la caracterizacion de la placa y evaluar la implantacion del stent en pacientes a los que se practican intervenciones coronarias percutaneas.

A case of lipid core plaque progression and rupture at the edge of a coronary stent: elucidating the mechanisms of drug-eluting stent failure.

Abstract: Received October 20, 2009; accepted January 20, 2010. Understanding the mechanisms of coronary drug-eluting stent (DES) failure remains relevant in light of concerns brought on by clinical reports of life-threatening late and very late stent thrombosis and by autopsy studies showing delayed and incomplete healing inside the stents, which may be related to underlying necrotic lipid core.1 Frequency-domain optical coherence tomography, also known as optical frequency-domain imaging (OFDI), is a new intracoronary imaging technology that enables 3-dimensional visualization of coronary structure in vivo at a resolution (≈6 μm) sufficient to identify many microscopic features of the coronary wall and stents.2 Here, we present a case of late DES failure that was imaged by OFDI at the time of stent implantation and 15 months later on presentation with unstable angina. The patient was a 52-year-old man with hypertension, dyslipidemia, a family history of coronary artery disease, and prior myocardial infarction in 1998. The patient presented again to the Lahey Clinic in 2007 (baseline), complaining of rest and exertional chest pain and with a positive stress test.2 Angiography revealed a 99% stenosis in the right coronary artery near the bifurcation of the posterior descending artery (Figure 1A). Deployment of a 3×18-mm sirolimus DES (Cypher Cordis, Miami, Fla) was performed with a good result (Figure 1B and 1C). The operators were blinded to the results of OFDI imaging. The patient was maintained on dual antiplatelet therapy (aspirin and clopidogrel) and a statin. The patient returned 15 months later with symptoms of unstable angina. Diagnostic angiography was performed, followed by OFDI of the right coronary artery. The angiogram revealed a 95% right …

Endoscopic biopsy apparatus, system and method

Abstract: Exemplary embodiments of apparatus, method and system for determining a position on or in a biological tissue can be provided. For example, using such exemplary embodiment, it is possible to control the focus of an optical imaging probe. In another exemplary embodiment, it is possible to implement a marking apparatus together with or into an optical imaging probe. According to one exemplary embodiment, it is possible (using one or more arrangements) to receive information associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique. Further, it is possible to, based on the information, cause a visible change on or in at least location of the portion(s) using at least one electro-magnetic radiation.

Heart wall velocimetry and exogenous contrast-based cardiac flow imaging in Drosophila melanogaster using Doppler optical coherence tomography

Abstract: Drosophila melanogaster (fruit fly) is a central organism in biology and is becoming increasingly important in the cardiovascular sciences. Prior work in optical imaging of the D. melanogaster heart has focused on static and dynamic structural anatomy. In the study, it is demonstrated that Doppler optical coherence tomography can quantify dynamic heart wall velocity and hemolymph flow in adult D. melanogaster. Since hemolymph is optically transparent, a novel exogenous contrast technique is demonstrated to increase the backscatter-based intracardiac Doppler flow signal. The results presented here open up new possibilities for functional cardiovascular phenotyping of normal and mutant D. melanogaster.

Compensation of motion artifacts in catheter-based optical frequency domain imaging

Abstract: A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging

Multimodality cardiovascular molecular imaging technology

Abstract: Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine.

Quantitative FRET measurement by high-speed fluorescence excitation and emission spectrometer.

Abstract: Forster resonance energy transfer (FRET) is an important method in studying biochemistry reactions. But quantifying FRET rapidly is difficult to do because of crosstalk between free donor, free acceptor and FRET fluorescent signals when only excitation or emission property of a FRET sample is measured. If FRET is studied with excitation-emission matrix (EEM) measurements, because the fluorescence intensity maxima of donor, acceptor, and FRET emissions occupy different regions within the EEM, FRET fluorescence can be easily separated out by linear unmixing. In this paper, we report a novel high-speed Fourier Fluorescence Excitation Emission spectrometer, which simultaneously measures three projections of EEM from a FRET sample, which are excitation, emission and excitation-emission cross-correlation spectra. We demonstrate that these three EEM projections can be measured and unmixed in approximately 1 ms to provide rapid quantitative FRET in the presence of free donors and acceptors. The system can be utilized to enable real-time biochemistry reaction studies.

An automatic image processing algorithm for initiating and terminating intracoronary OFDI pullback

Abstract: Intracoronary optical frequency domain imaging (OFDI) provides high resolution, three-dimensional views of coronary artery microstructure, but requires a non-occlusive saline/contrast purge to displace blood for clear artery views. Recent studies utilized manual pullback initiation/termination based on real-time image observation. Automated pullback initiation/termination by real-time OFDI signal analysis would enable more efficient data acquisition. We evaluate the use of simple imaging parameters to automatically and robustly differentiate between diagnostic-quality clear artery wall (CAW) versus blood-obstructed fields (BOF). Algorithms are tested using intracoronary OCT human data retrospectively and intracoronary OFDI swine and human data prospectively. In prospective analysis of OFDI swine data, the sensitivity and specificity of the ratio of second and first moments (contrast parameter) were 99.6% and 97.2%, respectively. In prospective analysis of OFDI clinical data, the contrast parameter yielded 96.0% sensitivity and 94.5% specificity. Accuracy improved further by analyzing sequential frames. These results indicate the algorithm may be utilized with intracoronary OFDI for initiating and terminating automated pullback and digital data recording.

Co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system

Abstract: Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.

Reflectance microscopy techniques for 3D imaging of the alveolar structure

Abstract: Lung disease involving the alveoli and distal bronchioles are poorly understood and most commonly studied indirectly via lung function tests. Available imaging tools for the non-destructive assessment of the alveolar structure include X-ray computed tomography, intra-vital fluorescence microscopy and Optical Coherence Tomography, which are either limited by long acquisition time, inadequate resolution and contrast, or shallow imaging depth. In this study, we investigated the potential of two high-resolution reflectance microscopy imaging techniques, Spectrally Encoded Confocal Microscopy (SECM; 1µm (x) x 1µm (y) x 5µm (z) resolution) and Full Field Optical Coherence Microscopy (FFOCM; 1µm (x) x 1µm (y) x 1µm (z) resolution), for imaging alveolar microstructural detail. Two mouse lung samples were imaged with both SECM and FFOCM. The specimens were inflation-fixed using a modified Heitzman fixation technique at 20 cm H2O pressure. They were cut in 500mm thick slices and water immersed for imaging. Images were obtained and analyzed to determine whether or not the resolution and contrast of these techniques are sufficient to visualize the fine structures of the alveolar wall. Alveolar microstructure could be resolved in three dimensions in images obtained by both technologies. Alveolar septal walls from multiple layers could be clearly identified while sub-cellular structures such as nuclei were also visible in the SECM technique. In conclusion, we have demonstrated that two imaging technologies provide important sub-cellular detail that is required to study alveolar microstructure. Future research to develop these imaging modalities further so that they may be used in vivo is merited.

Shedding Light on Bioabsorbable Stent Struts Seen by Optical Coherence Tomography in the ABSORB Trial

Abstract: Optical coherence tomography (OCT) is an emerging intracoronary imaging technology that obtains depth-resolved images of light backscattered from the coronary wall with an axial resolution of ≈10 μm. First demonstrated in 2001 in patients,1 intracoronary OCT is now commercially available and is beginning to be adopted in cardiac catheterization laboratories worldwide. An important application of OCT is the investigation of intracoronary stents; ≈100 articles have been published over the past 5 years in which OCT was used for this purpose. OCT is well suited for such studies because (1) its contrast and resolution enable delineation of fine details including device and arterial wall structures; (2) stent healing occurs near the luminal surface, where OCT is most effective; and (3) relative to other imaging modalities, OCT has fewer imaging artifacts that interfere with the appearance of stent struts and surrounding tissues. Article see p 2288 Recently, researchers have found that OCT may also be well suited for investigating the fate of bioabsorbable stents, including bioabsorbable vascular scaffolds (BVS).2,–,9 These new devices are of particular interest because they offer the potential to facilitate coronary revascularization while subsequently being dissolved and assimilated into the artery wall. Resorption in this manner may overcome many of the limitations of bare-metal and drug-eluting stents by leaving behind a revascularized coronary artery without any residual “foreign” material that can promote restenosis or precipitate late stent thrombosis. Given the recent introduction of new generations of bioabsorbable stents, it is critical to understand and monitor …

Three-dimensional microscopy of the human bronchial mucosa

Abstract: Lung cancer is the leading cause of cancer related death, and despite recent efforts to reduce the mortality associated with the disease, patient prognosis remains poor with the current 5-year survival rate under 15%. Detection and diagnosis of lesions arising in the bronchial mucosa remains problematic and as a result they are typically well advanced upon discovery.

Ultrahigh-resolution 3D full-field optical coherence micropscopy of the pulmonary airways ex vivo

Abstract: Visualizing the respiratory mucosa in pulmonary airways at the sub-cellular level could yield new insights into pathogenesis of many important diseases However, current imaging modalities to study the respiratory mucosa lack the required resolution to visualize critical subcellular detail such as nuclei and respiratory epithelial cilia Full-field optical coherence microscopy (FFOCM) is an emerging technique capable of providing reflectance images in situ with high spatial resolution in all three dimensionsWe have developed a FFOCM with an axial sectioning thickness of 1µm and a high transverse resolution of 06µm The three-dimensional field of view was 256 (H) x 256 (W) x 400 (D) µm Three-dimensional images of formalin-fixed, sectioned porcine bronchial segments were obtained immediately ex vivo Images were compared to H&E stained histology at corresponding sites Pilot images on fixed human airways from individuals with cystic fibrosis (CF) and Chronic Obstructive Pulmonary Disease (COPD) were also acquired Individual epithelial cells and goblet cells, including their subcellular morphologies, were easily seen Cross-sectional views showed gland ducts containing mucus, cilia, the periciliary layer (PCL), and nuclei Three-dimensional rendering of the trachea showed the presence of mucus droplets directly above non-ciliated goblet cells, tethered to the surface of these cells by a thin adherent mucus strand Our results demonstrate the potential of FFOCM to provide detailed microstructural imaging of pulmonary airways without administration of a contrast medium The future development of a probe for in vivo monitoring of mucociliary transport, gland function, and airway surface liquid (ASL) depth could provide new avenues for improving our understanding of respiratory mucosal pathophysiology and enable longitudinal assessment of the response to novel drugs

High-speed three-dimensional imaging of the pulmonary alveoli

Abstract: Investigating the structure and function of pulmonary alveoli in vivo is crucial for understanding the normal and diseased lung. In particular, understanding the three-dimensional geometry and relationship of the terminal alveoli to their neighboring alveoli, alveolar ducts and acini during respiration would be a major advance. However, the lung is an inherently difficult organ to image in vivo and the peripheral lung has many compounding challenges not limited to its highly scattering micro architecture, large motion artifacts and difficult access through the bronchial tree. In this study, we image the alveoli of fixed pig lungs using a high-speed high-resolution optical frequency domain imaging (OFDI) system that is endoscopically compatible for future in vivo imaging of human alveoli. Core imaging components include a rapidly swept wavelength source centered at 1310nm resulting in an A-line depth scan rate of 62,500Hz, a polarization diverse dual balanced receiver, and a high speed data acquisition system. Whole lungs were excised from normal piglets and inflation fixed at 15cm H2O pressure using a modified Heitzman fixation technique. Lungs were air dried in a heated oven and sectioned into 500µm slices. Three-dimensional datasets were acquired from lung slices with 512x512x1024 voxels and a voxel dimension of 5x5x8µm. Datasets were acquired at 122 frames per second and 0.23 volumes per second - indicating the potential to acquire a three-dimensional volume within a single human respiratory cycle. OFDI images reveal clear delineation of alveolar septal walls, demonstrating that high-speed three-dimensional visualization of air filled alveoli is feasible. The fixed lung data provides a strong foundation for investigating the 3D structure and function of alveoli in vivo and suggests great promise for advancing our knowledge of the functional unit of the lung.

In vivo imaging of microvasculature using optical coherence tomography

Abstract: Summary In vivo imaging technologies drive the development of improved cancer therapies by revealing critical aspects of the complex pathophysiology of solid tumors in small animal models[1]. The abnormal vascular function, which predicts tumor malignant potential and presents broad barriers to effective treatment, has been studied at the subcellular size scale using multiphoton (MP) microscopy [2], and at significantly larger size scales using ultrasound, µCT and µMRI[3–5]. However, limited in vivo imaging approaches exist to study the vascular function at the network level, i.e., with sufficient resolution to discern smaller vessels while maintaining a field of view and penetration depth large enough to reveal interconnectivity and inhomogeneities across the tumor and surrounding tissue. One promising technology operating at this size scale is optical frequency domain imaging (OFDI) using Doppler-methods to detect blood flow.

Challenges on the frontier of intracoronary imaging: atherosclerotic plaque macrophage measurement by optical coherence tomography

Abstract: Cellularity of the fibrous caps of coronary atheromas, manifested by the infiltration of macrophages (average size, 20 to 30 microm), is thought to weaken the structural integrity of the cap and predispose plaques to rupture. Therefore, an imaging technology capable of identifying macrophages within fibroatheroma caps in patients could provide valuable information for assessing plaque rupture risk. Recently, intravascular optical coherence tomography (OCT), a high-resolution coronary imaging modality, with an axial resolution of approximately 10 microm, has been introduced into the clinical setting. OCT images of the microstructure of the coronary artery wall enable accurate plaque-type characterization, supported by histopathological comparison data. Because of its high resolution, OCT may also be used to identify macrophages in vivo. In this paper we review recent developments in OCT for measuring macrophages in atherosclerotic plaques.