Showing papers by "Brett E. Bouma published in 2008"

Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging.

Abstract: Objectives We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients Background Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (∼7-μm axial resolution, ∼30-μm transverse resolution), cross-sectional images of the coronary wall Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge Methods Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered Results Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 30 to 70 cm at pullback rates ranging from 5 to 20 mm/s A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia There were no complications of the OFDI procedure Conclusions Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease

High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing

Abstract: Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm.

In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography.

Abstract: Aims Positive coronary arterial remodelling has been shown to be associated with unstable coronary syndromes and ex vivo histological characteristics of plaque vulnerability such as a large lipid core and high macrophage content. The aim of this study is to evaluate the in vivo association between coronary artery remodelling and underlying plaque characteristics identified by optical coherence tomography (OCT). OCT is a unique imaging modality capable of characterizing these important morphological features of vulnerable plaque. Methods and results OCT and intravascular ultrasound imaging was performed at corresponding sites in patients undergoing catheterization. OCT plaque characteristics for lipid content, fibrous cap thickness, and macrophage density were derived using previously validated criteria. Thin-cap fibroatheroma (TCFA) was defined as lipid-rich plaque (two or more quadrants) with fibrous cap thickness <65 µm. Remodelling index (RI) was calculated as the ratio of the lesion to the reference external elastic membrane area. A total of 54 lesions from 48 patients were imaged. Positive remodelling compared with absent or negative remodelling was more commonly associated with lipid-rich plaque (100 vs. 60 vs. 47.4%, P = 0.01), a thin fibrous cap (median 40.2 vs. 51.6 vs. 87 µm, P = 0.003) and the presence of TCFA (80 vs. 38.5 vs. 5.6%, P < 0.001). Fibrous cap macrophage density was also higher in plaques with positive remodelling showing a positive linear correlation with the RI ( r = 0.60, P < 0.001). Conclusion Coronary plaques with positive remodelling exhibit characteristic features of vulnerable plaque. This may explain the link between positive remodelling and unstable clinical presentations.

Estimation of nonlinear mechanical properties of vascular tissues via elastography

Abstract: A new method is proposed for estimation of nonlinear elastic properties of soft tissues. The proposed approach involves a combination of nonlinear finite element methods with a genetic algorithm for estimating tissue stiffness profile. A multipoint scheme is introduced that satisfies the uniqueness condition, improves the estimation performance, and reduces the sensitivity to image noise. The utility of the proposed techniques is demonstrated using optical coherence tomography (OCT) images. The approach is, however, applicable to other imaging systems and modalities, as well, provided a reliable image registration scheme. The proposed algorithm is applied to realistic (2D) and idealized (3D) arterial plaque models, and proves promising for the estimation of intra-plaque distribution of nonlinear material properties.

Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance

Abstract: Fine needle aspiration biopsy FNAB is a rapid and cost-effective method for obtaining a first-line diagno- sis of a palpable mass of the breast. However, because it can be difficult to manually discriminate between adipose tissue and the fibroglandular tissue more likely to harbor disease, this technique is plagued by a high number of nondiagnostic tissue draws. We have developed a por- table, low coherence interferometry LCI instrument for FNAB guidance to combat this problem. The device con- tains an optical fiber probe inserted within the bore of the fine gauge needle and is capable of obtaining tissue struc- tural information with a spatial resolution of 10 m over a depth of approximately 1.0 mm. For such a device to be effective clinically, algorithms that use the LCI data must be developed for classifying different tissue types. We present an automated algorithm for differentiating adipose tissue from fibroglandular human breast tissue based on three parameters computed from the LCI signal slope, standard deviation, spatial frequency content. A total of 260 breast tissue samples from 58 patients were collected from excised surgical specimens. A training set N=72 was used to extract parameters for each tissue type and the parameters were fit to a multivariate normal density. The model was applied to a validation set N=86 using like- lihood ratios to classify groups. The overall accuracy of the model was 91.9% 84.0 to 96.7 with 98.1% 89.7 to 99.9 sensitivity and 82.4% 65.5 to 93.2 specificity where the numbers in parentheses represent the 95% con- fidence intervals. These results suggest that LCI can be used to determine tissue type and guide FNAB of the breast. © 2008 Society of Photo-Optical Instrumentation Engineers.

Association of statin therapy with reduced coronary plaque rupture: an optical coherence tomography study.

Abstract: OBJECTIVE Statin therapy induces plaque regression and may stabilize atheromatous plaques. Optical coherence tomography (OCT) is a high-resolution in-vivo imaging modality that allows characterization of atherosclerotic plaques. We aimed to demonstrate the potential utility of OCT in evaluating coronary plaques in patients with or without statin therapy. METHODS Patients undergoing cardiac catheterization were enrolled. We identified culprit lesions and performed intracoronary OCT imaging. Plaque lipid pool, fibrous cap thickness, and frequency of thin-cap fibroatheroma were evaluated using previously validated criteria. Macrophage density was determined from optical signals within fibrous caps. Presence of calcification, thrombosis, and rupture was assessed. RESULTS Forty-eight patients were included (26 on statins, 22 without statins). Baseline characteristics were similar apart from lipid profile. Patients on statin therapy had lower total and low-density lipoprotein cholesterol concentrations (4.45+/-1.35 vs. 5.26+/-0.83 mmol/l, P=0.02; 2.23+/-0.78 vs. 3.26+/-0.62 mmol/l, P<0.001, respectively). Frequencies of lipid-rich plaque (69 vs. 82%), thin-cap fibroatheroma (31 vs. 50%), plaque calcification (15 vs. 5%) and thrombosis (15 vs. 32%), and fibrous cap macrophage density were comparable between statin and nonstatin groups (5.9 vs. 6.3%; all P=NS). Ruptured plaques were, however, significantly less frequent in patients on established statin therapy (8 vs. 36%; P=0.03) with a trend toward increased minimum fibrous cap thickness (78 vs. 49 microm; P=0.07). CONCLUSION We demonstrated the use of OCT in plaque characterization and found that patients on prior statin therapy have reduced incidence of ruptured plaques and a trend toward thicker fibrous caps. This suggests that statins may stabilize coronary plaques.

Laser speckle imaging of atherosclerotic plaques through optical fiber bundles.

Abstract: Laser speckle imaging (LSI), a new technique that measures an index of plaque viscoelasticity, has been investigated recently to characterize atherosclerotic plaques. These prior studies demonstrated the diagnostic potential of LSI for detecting high-risk plaques and were conducted ex vivo. To conduct intracoronary LSI in vivo, the laser speckle pattern must be transmitted from the coronary wall to the image detector in the presence of cardiac motion. Small-diameter, flexible optical fiber bundles, similar to those used in coronary angioscopy, may be incorporated into an intravascular catheter for this purpose. A key challenge is that laser speckle is influenced by inter-fiber leakage of light, which may be exacerbated during bundle motion. In this study, we tested the capability of optical fiber bundles to transmit laser speckle patterns obtained from atherosclerotic plaques and evaluated the influence of motion on the diagnostic accuracy of fiber bundle-based LSI. Time-varying helium-neon laser speckle images of aortic plaques were obtained while cyclically moving the flexible length of the bundle to mimic coronary motion. Our results show that leached fiber bundles may reliably transmit laser speckle images in the presence of cardiac motion, providing a viable option to conduct intracoronary LSI.

System and method providing intracoronary laser speckle imaging for the detection of vulnerable plaque

Abstract: Apparatus and method according to an exemplary embodiment of the present invention can be provided for analyzing tissue. For example, the apparatus can include at least one first arrangement configured to illuminate at least one anatomical structure with at least one of at least one electro-magnetic radiation. The apparatus can also include at least one second arrangement that may include at least two wave-guiding arrangements associated with one another that are configured to receive a further electro-magnetic radiation reflected from the tissue and transmit at least one speckle pattern associated with the further electro-magnetic radiation. The wave-guiding arrangements may be structured so as to reduce crosstalk therebetween.

Single-detector polarization-sensitive optical frequency domain imaging using high-speed intra A-line polarization modulation.

Abstract: We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample.

Volumetric sub-surface imaging using spectrally encoded endoscopy

Abstract: Endoscopic imaging below tissue surfaces and through turbid media may provide improved diagnostic capabilities and visibility in surgical settings. Spectrally encoded endoscopy (SEE) is a recently developed method that utilizes a single optical fiber, miniature optics and a diffractive grating for high-speed imaging through small diameter, flexible endoscopic probes. SEE has also been shown to provide three-dimensional topological imaging capabilities. In this paper, we have configured SEE to additionally image beneath tissue surfaces, by increasing the system’s sensitivity and acquiring the complex spectral density for each spectrally resolved point on the sample. In order to demonstrate the capability of SEE to obtain subsurface information, we have utilized the system to image a resolution target through intralipid solution, and conduct volumetric imaging of a mouse embryo and excised human middle-ear ossicles. Our results demonstrate that real-time subsurface imaging is possible with this miniature endoscopy technique.

Fingerprint and high-wavenumber Raman spectroscopy in a human-swine coronary xenograft in vivo

Abstract: Intracoronary Raman spectroscopy could open new avenues for the study and management of coronary artery disease due to its potential to measure the chemical and molecular composition of coronary atherosclerotic le- sions. We have fabricated and tested a 1.5-mm-diameter 4.5 Fr Raman catheter capable of collecting Raman spectra in both the fingerprint 400-1800 cm �1 and high-wavenumber 2400-3800 cm �1 regions. Spectra were acquired in vivo, using a human-swine xenograft model, in which diseased human coronary arteries are grafted onto a living swine heart, replicating the disease and dynamic environment of the human circulatory sys- tem, including pulsatile flow and motion. Results show that distinct spectral differences, corresponding to the morphology and chemical composition of the artery wall, can be identified by intracoronary Raman spectroscopy in vivo. © 2008 Society of Photo-Optical Instrumentation Engineers.

Doppler imaging using spectrally-encoded endoscopy

Abstract: The capability to image tissue motion such as blood flow through an endoscope could have many applications in medicine Spectrally encoded endoscopy (SEE) is a recently introduced technique that utilizes a single optical fiber and miniature diffractive optics to obtain endoscopic images through small diameter probes Using spectral-domain interferometry, SEE is furthermore capable of three-dimensional volume imaging at video rates Here we show that by measuring relative spectral phases, this technology can additionally measure Doppler shifts Doppler SEE is demonstrated in flowing Intralipid phantoms and vibrating middle ear ossicles

Fingerprint and high-wavenumber Raman spectroscopy in a human-swine coronary xenograft in vivo

Abstract: Intracoronary Raman spectroscopy could open new avenues for the study and management of coronary artery disease due to its potential to measure the chemical and molecular composition of coronary atherosclerotic le- sions. We have fabricated and tested a 1.5-mm-diameter 4.5 Fr Raman catheter capable of collecting Raman spectra in both the fingerprint 400-1800 cm �1 and high-wavenumber 2400-3800 cm �1 regions. Spectra were acquired in vivo, using a human-swine xenograft model, in which diseased human coronary arteries are grafted onto a living swine heart, replicating the disease and dynamic environment of the human circulatory sys- tem, including pulsatile flow and motion. Results show that distinct spectral differences, corresponding to the morphology and chemical composition of the artery wall, can be identified by intracoronary Raman spectroscopy in vivo. © 2008 Society of Photo-Optical Instrumentation Engineers.

Fluorescence interferometry: principles and applications in biology.

Abstract: The use of fluorescence radiation is of fundamental importance for tackling measurement problems in the life sciences, with recent demonstrations of probing biological systems at the nanoscale. Usually, fluorescent light-based tools and techniques use the intensity of light waves, which is easily measured by detectors. However, the phase of a fluorescence wave contains subtle, but no less important, information about the wave; yet, it has been largely unexplored. Here, we introduce the concept of fluorescence interferometry to allow the measurement of phase information of fluorescent light waves. In principle, fluorescence interferometry can be considered a unique form of optical low-coherence interferometry that uses fluorophores as a light source of low temporal coherence. Fluorescence interferometry opens up new avenues for developing new fluorescent light-based imaging, sensing, ranging, and profiling methods that to some extent resemble interferometric techniques based on white light sources. We propose two experimental realizations of fluorescence interferometry that detect the interference pattern cast by the fluorescence fields. This article discusses their measurement capabilities and limitations and compares them with those offered by optical low-coherence interferometric schemes. We also describe applications of fluorescence interferometry to imaging, ranging, and profiling tasks and present experimental evidences of wide-field cross-sectional imaging with high resolution and large range of depth, as well as quantitative profiling with nanometer-level precision. Finally, we point out future research directions in fluorescence interferometry, such as fluorescence tomography of whole organisms and the extension to molecular interferometry by means of quantum dots and bioluminescence.

Fourier fluorescence spectrometer for excitation emission matrix measurement

Abstract: We demonstrate a fluorescence spectrometer that utilizes principles of Fourier transform spectroscopy to measure excitation emission matrices (EEM) rapidly and with high spectral resolution. For this EEM fluorometer, incoherent excitation light is first input into a differential-delay scanning Michelson interferometer. Light from the output port excites sample fluorescence. The fluorescence remitted from the sample is directed to a second Michelson interferometer, whose differential-delay scanning is synchronized with the first interferometer. The EEM is obtained by two-dimensional Fourier analysis of the detected signal from the output port of the second interferometer. EEM results from the system are verified by comparing with results from a standard spectrometer. The system provides a wide spectral range, adjustable spectral resolution, and fast EEM acquisition speed, which allows EEM’s to be acquired in 40 seconds at a spectral resolution of 81-cm-1.

Interferometric Spectrally Encoded Endoscopy

Abstract: Using low coherence interferometry, spectrally encoded endoscopy (SEE) is capable of volumetric subsurface reflectance and Doppler imaging The technique is demonstrated by imaging a variety of samples through miniature fiber optic endoscopic probes

Differential near-field scanning optical microscopy based on sensor arrays

Abstract: We introduce a new aperture-type near-field scanning optical microscopy (NSOM) system, which rely on large area (e.g., > 200 x 200 nm) aperture geometries that have sharp corners. The spatial resolution of this new near-field imaging modality is not determined by the size of the aperture, but rather by the sharpness of the corners of the large aperture. This approach significantly improves the light throughput of the near-field probe and therefore increases the optical signal-to-noise ratio (SNR). Here we discuss the basics of this new near-field microscopy approach and illustrate both theoretically and experimentally that an array of detectors can be utilized to further improve the SNR of the near-field image.

Automated algorithm for differentiation of human breast tissue using low coherence interferometry for fine needle aspiration biopsy guidance

Abstract: Fine needle aspiration biopsy FNAB is a rapid and cost-effective method for obtaining a first-line diagno- sis of a palpable mass of the breast. However, because it can be difficult to manually discriminate between adipose tissue and the fibroglandular tissue more likely to harbor disease, this technique is plagued by a high number of nondiagnostic tissue draws. We have developed a por- table, low coherence interferometry LCI instrument for FNAB guidance to combat this problem. The device con- tains an optical fiber probe inserted within the bore of the fine gauge needle and is capable of obtaining tissue struc- tural information with a spatial resolution of 10 m over a depth of approximately 1.0 mm. For such a device to be effective clinically, algorithms that use the LCI data must be developed for classifying different tissue types. We present an automated algorithm for differentiating adipose tissue from fibroglandular human breast tissue based on three parameters computed from the LCI signal slope, standard deviation, spatial frequency content. A total of 260 breast tissue samples from 58 patients were collected from excised surgical specimens. A training set N=72 was used to extract parameters for each tissue type and the parameters were fit to a multivariate normal density. The model was applied to a validation set N=86 using like- lihood ratios to classify groups. The overall accuracy of the model was 91.9% 84.0 to 96.7 with 98.1% 89.7 to 99.9 sensitivity and 82.4% 65.5 to 93.2 specificity where the numbers in parentheses represent the 95% con- fidence intervals. These results suggest that LCI can be used to determine tissue type and guide FNAB of the breast. © 2008 Society of Photo-Optical Instrumentation Engineers.