Biomedical subjects

Brett E Bouma

Publications and source records attributed to Brett E Bouma.

At least 19 recordsLinked to original sources

PubMed2006

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Angioplasty↗

PubMed2006

Identifying intestinal metaplasia at the squamocolumnar junction by using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) is an optical imaging method that produces high-resolution cross-sectional images of the esophagus. The accuracy of OCT for differentiating tissue types at the squamocolumnar junction (SCJ) has not been established. OBJECTIVE: The purpose of this study was to identify and validate OCT image criteria for distinguishing metaplastic from nonmetaplastic tissue at the SCJ. DESIGN: A total of 196 biopsy-correlated OCT images of the SCJ were acquired from 113 patients undergoing upper endoscopy. A pathologist blinded to the OCT results reviewed each pathology specimen and determined the presence of the following histopathology: gastric cardia, squamous mucosa, pancreatic metaplasia, and intestinal metaplasia. An algorithm for diagnosing specialized intestinal metaplasia (SIM) was created by reviewing a training set of 40 biopsy-correlated OCT images. Two blinded investigators prospectively tested the algorithm on a validation set of 123 images. RESULTS: OCT images of squamous mucosa were characterized by a layered appearance without epithelial glands; gastric cardia, by vertical pit and gland structure, a well-defined epithelial surface reflectivity, and relatively poor image penetration; and SIM by an irregular architecture and good image penetration. The OCT criteria were 85% sensitive and 95% specific for SIM when applied retrospectively to the training set. When applied to the validation set, the algorithm was 81% sensitive for both OCT readers and 66% and 57% specific for diagnosing SIM. The interobserver agreement was good (kappa = 0.53). CONCLUSIONS: OCT imaging can identify SIM at the SCJ with an accuracy similar to that of endoscopy.

Algorithms↗

PubMed2006

Arterial wall imaging: evaluation with 16-section multidetector CT in blood vessel phantoms and ex vivo coronary arteries.

PURPOSE: To evaluate the diagnostic performance of 16-section multidetector computed tomography (CT) for assessment of plaques in phantoms and ex vivo coronary arteries, with intravascular ultrasonography (US) and optical coherence tomography (OCT) as reference standards. MATERIALS AND METHODS: Research protocol was HIPAA compliant and approved by institutional review board, without informed consent required. Blood vessel and lesion composition phantoms and ex vivo coronary arteries were imaged with 16-section CT. Wall areas of phantoms and ex vivo coronary arteries were measured with multidetector CT and intravascular US. Sensitivity and specificity for lipid detection were determined in lesion composition phantoms. CT numbers of blood vessel wall were determined in ex vivo coronary arteries and compared with lesion classification results from OCT. Agreement in dimensional measurements was compared (paired t tests). CT numbers within blood vessel wall of CT cross sections classified as lipid rich, fibrous, and calcified at OCT were compared (Kruskal-Wallis tests). RESULTS: Mean blood vessel wall areas measured with CT and US in phantoms were 9.2 mm(2) +/- 1.8 (standard deviation) and 10.4 mm(2) +/- 3.4 (bias, -1.3 mm(2) +/- 3.1; P < .05), respectively. Mean blood vessel wall areas measured in ex vivo coronary arteries with CT and US were 10.9 mm(2) +/- 4.1 and 9.1 mm(2) +/- 3.1 (bias, 1.8 mm(2) +/- 3.0; P < .001), respectively. Sensitivity and specificity of 93% and 92%, respectively, for identification of lipid-rich lesions were observed in lesion composition phantoms. Mean CT numbers in blood vessel wall of ex vivo coronary arteries identified at OCT as predominantly lipid rich, fibrous, and calcified were 29 HU +/- 43, 101 HU +/- 21, and 135 HU +/- 199, respectively (P < .001). CONCLUSION: Determination of composition of individual plaques from attenuation values can be more challenging because of overlapping values for different tissue types.

Coronary Angiography↗

PubMed2006

Diagnostic accuracy of optical coherence tomography and integrated backscatter intravascular ultrasound images for tissue characterization of human coronary plaques.

OBJECTIVES: The purpose of the present study was to validate the diagnostic accuracy of optical coherence tomography (OCT), integrated backscatter intravascular ultrasound (IB-IVUS), and conventional intravascular ultrasound (C-IVUS) for tissue characterization of coronary plaques and to evaluate the advantages and limitations of each of these modalities. BACKGROUND: The diagnostic accuracy of OCT for characterizing tissue types is well established. However, comparisons among OCT, C-IVUS, and IB-IVUS have not been done. METHODS: We examined 128 coronary arterial sites (42 coronary arteries) from 17 cadavers; IVUS and OCT images were acquired on the same slice as histology. Ultrasound signals were obtained using an IVUS system with a 40-MHz catheter and digitized at 1 GHz with 8-bit resolution. The IB values of the ultrasound signals were calculated with a fast Fourier transform. RESULTS: Using histological images as a gold standard, the sensitivity of OCT for characterizing calcification, fibrosis, and lipid pool was 100%, 98%, and 95%, respectively. The specificity of OCT was 100%, 94%, and 98%, respectively (Cohen's kappa = 0.92). The sensitivity of IB-IVUS was 100%, 94%, and 84%, respectively. The specificity of IB-IVUS was 99%, 84%, and 97%, respectively (Cohen's kappa = 0.80). The sensitivity of C-IVUS was 100%, 93%, and 67%, respectively. The specificity of C-IVUS was 99%, 61%, and 95%, respectively (Cohen's kappa = 0.59). CONCLUSIONS: Within the penetration depth of OCT, OCT has a best potential for tissue characterization of coronary plaques. Integrated backscatter IVUS has a better potential for characterizing fibrous lesions and lipid pools than C-IVUS.

Calcinosis↗

PubMed2006

A combined FEM/genetic algorithm for vascular soft tissue elasticity estimation.

Tissue elasticity reconstruction is a parameter estimation effort combining imaging, elastography, and computational modeling to build maps of soft tissue mechanical properties. One application is in the characterization of atherosclerotic plaques in diseased arteries, wherein the distribution of elastic properties is required for stress analysis and plaque stability assessment. In this paper, a computational scheme is proposed for elasticity reconstruction in soft tissues, combining finite element modeling (FEM) for mechanical analysis of soft tissues and a genetic algorithm (GA) for parameter estimation. With a model reduction of the discrete elasticity values into lumped material regions, namely the plaque constituents, a robust, adaptive strategy can be used to solve inverse elasticity problems involving complex and inhomogeneous solution spaces. An advantage of utilizing a GA is its insistence on global convergence. The algorithm is easily implemented and adaptable to more complex material models and geometries. It is meant to provide either accurate initial guesses of low-resolution elasticity values in a multi-resolution scheme or as a replacement for failing traditional elasticity estimation efforts.

Algorithms↗

PubMed2006

Differential near-field scanning optical microscopy.

We theoretically and experimentally illustrate a new apertured near-field scanning optical microscopy (NSOM) technique, termed differential NSOM (DNSOM). It involves scanning a relatively large (e.g., 0.3-2 mum wide) rectangular aperture (or a detector) in the near-field of an object and recording detected power as a function of the scanning position. The image reconstruction is achieved by taking a two-dimensional derivative of the recorded power map. Unlike conventional apertured NSOM, the size of the rectangular aperture/detector does not determine the resolution in DNSOM; instead, the resolution is practically determined by the sharpness of the corners of the rectangular aperture/detector. Principles of DNSOM can also be extended to other aperture/detector geometries such as triangles and parallelograms.

Equipment Design↗

PubMed2006

Technology Insight: optical coherence tomography--current status and future development.

The understanding of concepts in coronary artery disease, such as the vulnerable or high-risk plaque, which accounts for many acute coronary events arising from non-flow-limiting coronary lesions, has advanced remarkably. Although coronary angiography is an established imaging technique for visualizing atherosclerotic disease, it is limited by its two-dimensional imaging aspect and a low sensitivity for identifying lesions in the presence of positive remodeling and diffuse disease. Moreover, coronary atherosclerotic plaques cannot be characterized. Although intravascular ultrasound is currently the most commonly employed adjunctive method to better define lesions, it is limited by low resolution. The development of new technologies for improved coronary plaque characterization has, thus, been desired. Optical coherence tomography is a developing technique that uses near-infrared light for the cross-sectional visualization of the vessel wall at the microscopic level. It enables excellent resolution of coronary architecture and precise characterization of plaque architecture. Quantification of macrophages within the plaque is also possible. These capabilities allow precise identification of the most common type of vulnerable plaque, the thin-cap fibroatheroma. Here, we discuss results from clinical studies which indicate that optical coherence tomography is a promising imaging technique for improved characterization of the coronary atherosclerotic plaque.

Animals↗

PubMed2006

Optical coherence tomography to identify intramucosal carcinoma and high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Optical coherence tomography (OCT) is an optical technique that produces high-resolution images of the esophagus during endoscopy. OCT can distinguish specialized intestinal metaplasia (SIM) from squamous mucosa, but image criteria for differentiating intramucosal carcinoma (IMC) and high-grade dysplasia (HGD) from low-grade dysplasia (LGD), indeterminate-grade dysplasia (IGD), and SIM without dysplasia have not been validated. The purpose of this study was to establish OCT image characteristics of IMC and HGD in Barrett's esophagus. METHODS: Biopsy-correlated OCT images were acquired from patients with Barrett's esophagus undergoing endoscopic surveillance. Two pathologists rendered consensus diagnoses of the biopsy specimens. A blinded investigator reviewed the biopsy-correlated OCT images and scored each for surface maturation and gland architecture. For each image the scores were summed to determine an OCT "dysplasia index." RESULTS: A total of 177 biopsy-correlated images were analyzed. The corresponding histopathology diagnosis was IMC/HGD in 49 cases, LGD in 15, IGD in 8, SIM in 100, and gastric mucosa in 5. A significant relationship was found between a histopathologic diagnosis of IMC/HGD and scores for each image feature (dysplasia index [Spearman correlation coefficient, r = 0.50, P < .0001], surface maturation [r = 0.48, P < .0001], and gland architecture [r = 0.41, P < .0001]). When a dysplasia index threshold of >or=2 was used, the sensitivity and specificity for diagnosing IMC/HGD were 83% and 75%, respectively. CONCLUSIONS: An OCT image scoring system based on histopathologic characteristics has the potential to identify IMC and HGD in Barrett's esophagus.

Adult↗

PubMed2005

Spectral- and frequency-encoded fluorescence imaging.

A method for obtaining fluorescence images with a high number of resolvable points by using spectral and frequency encoding is presented. Broadband excitation light is encoded with a wavelength-dependent frequency modulation and dispersed onto the sample with a grating to simultaneously illuminate an entire image line. The Fourier transform of the frequency-encoded fluorescence emission provides one line of the image. Mechanical scanning along a direction orthogonal to the wavelength-encoded axis allows creation of the two-dimensional fluorescent image. This method is applicable for developing submillimeter diameter endoscopes. The principles of the technique are validated by imaging indocyanine green fluorescence in microfluidic channels.

Endoscopes↗

PubMed2005

Characterization of atherosclerotic plaques by laser speckle imaging.

BACKGROUND: A method capable of determining atherosclerotic plaque composition and measuring plaque viscoelasticity can provide valuable insight into intrinsic features associated with plaque rupture and can enable the identification of high-risk lesions. In this article, we describe a new optical technique, laser speckle imaging (LSI), that measures an index of plaque viscoelasticity. We evaluate the potential of LSI for characterizing atherosclerotic plaque. METHODS AND RESULTS: Time-varying helium-neon laser speckle images were acquired from 118 aortic plaque specimens from 14 human cadavers under static and deforming conditions (0 to 200 microm/s). Temporal fluctuations in the speckle patterns were quantified by exponential fitting of the normalized cross-correlation of sequential frames in each image series of speckle patterns to obtain the exponential decay time constant, tau. The decorrelation time constants of thin-cap fibroatheromas (TCFA) (tau=47.5+/-19.2 ms) were significantly lower than those of other atherosclerotic lesions (P<0.001), and the sensitivity and specificity of the LSI technique for identifying TCFAs were >90%. Speckle decorrelation time constants demonstrated strong correlation with histological measurements of plaque collagen (R=0.73, P<0.0001), fibrous cap thickness (R=0.87, P<0.0001), and necrotic core area (R=-0.81, P<0.0001). Under deforming conditions (10 to 200 microm/s), tau correlated well with cap thickness in necrotic core fibroatheromas (P>0.05). CONCLUSIONS: The measurement of speckle decorrelation time constant from laser speckle images provides an index of plaque viscoelasticity and facilitates the characterization of plaque type. Our results demonstrate that LSI is a highly sensitive technique for characterizing plaque and identifying thin-cap fibroatheromas.

Analysis of Variance↗

PubMed2005

In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography.

BACKGROUND: The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution ( approximately 10 microm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. METHODS AND RESULTS: Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non-ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying > or =2 quadrants of the cross-sectional area) was observed in 90%, 75%, and 59%, respectively (P=0.09). The median value of the minimum thickness of the fibrous cap was 47.0, 53.8, and 102.6 microm, respectively (P=0.034). The frequency of thin-cap fibroatheroma (defined by lipid-rich plaque with cap thickness < or =65 microm) was 72% in the AMI group, 50% in the ACS group, and 20% in the SAP group (P=0.012). No procedure-related complications occurred. CONCLUSIONS: OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo. Thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP. This is the first study to compare detailed in vivo plaque morphology in patients with different clinical presentations.

Aged↗

PubMed2005

Spectral domain optical coherence tomography: ultra-high speed, ultra-high resolution ophthalmic imaging.

OBJECTIVE: To introduce a new ophthalmic optical coherence tomography technology that allows unprecedented simultaneous ultra-high speed and ultra-high resolution. METHODS: Using a superluminescent diode source, a clinically viable ultra-high speed, ultra-high resolution spectral domain optical coherence tomography system was developed. RESULTS: In vivo images of the retina, the optic nerve head, and retinal blood flow were obtained at an ultra-high speed of 34.1 microseconds (ms) per A-scan, which is 73 times faster than commercially available optical coherence tomography instruments. Single images (B-scans) consisting of 1000 A-scans were acquired in 34.1 ms, allowing video rate imaging at 29 frames per second with an axial resolution of 6 mum. Using a different source in a slightly slower configuration, single images consisting of 500 A-scans were acquired in 34 ms, allowing imaging at 29 frames per second at an axial resolution of 3.5 microm, which is 3 times better than commercially available optical coherence tomography instruments. The amount of energy directed into the eye in both cases, 600 microW, is less than that of the Stratus OCT3 and is safe for intrabeam viewing for up to 8 hours at the same retinal location. CONCLUSION: Spectral domain optical coherence tomography technology enables ophthalmic imaging with unprecedented simultaneous ultra-high speed and ultra-high resolution.

Adult↗

PubMed2005

Optical coherence tomography as a tool for percutaneous coronary interventions.

This study was performed to demonstrate the ability of intravascular optical coherence tomography (OCT) to identify characteristic vascular responses to percutaneous coronary interventions (PCI). OCT provides cross-sectional images of tissue in situ at approximately 10 microm, rendering detailed structural information. Intravascular ultrasound and OCT images were obtained from 10 patients before and after PCI. Images were evaluated to identify balloon-induced dissections/disruptions, thrombus, cutting balloon-induced vascular changes, tissue protrusion, stent apposition and symmetry, and intimal hyperplasia. The disrupted intima, intraluminal thrombus, depth of balloon-induced dissections, cutting balloon cuts, tissue prolapse, underdeployed struts, and intimal hyperplasia were all noticed with OCT. This is the first report of the use of OCT to identify in vivo human intracoronary pathology after PCI.

Angioplasty, Balloon, Coronary↗

PubMed2005

Tissue elasticity estimation with optical coherence elastography: toward mechanical characterization of in vivo soft tissue.

High-resolution imaging provides a significant means for accurate material modulus estimation and mechanical characterization. Within the realm of in vivo soft tissue characterization, particularly on small biological length scales such as arterial atherosclerotic plaques, optical coherence tomography (OCT) offers a desirable imaging modality with higher spatial resolution and contrast of tissue as compared with intravascular ultrasound (IVUS). Based on recent advances in OCT imaging and elastography, we present a fully integrated system for tissue elasticity reconstruction, and assess the benefits of OCT on the distribution results of four representative tissue block models. We demonstrate accuracy, with displacement residuals on the order of 10(-6) mm (more than 3 orders of magnitude less than average calculated displacements), and high-resolution estimates, with the ability to resolve inclusions of 0.15 mm diameter.

Angiography↗

PubMed2004

Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease.

OBJECTIVES: This study was designed to utilize optical coherence tomography (OCT) images of coronary atherosclerotic plaque macrophages to investigate the relationship between macrophage distributions and clinical syndrome. BACKGROUND: The relative significance of focal macrophage infiltration and generalized coronary inflammation for predicting acute coronary events is a currently a source of considerable controversy in cardiology. Lack of a high-resolution cross-sectional imaging modality has limited macrophage evaluation in vivo. METHODS: Intracoronary OCT imaging was performed at culprit and non-culprit plaques in patients presenting with stable angina pectoris, unstable angina pectoris,and ST-segment elevation myocardial infarction. Macrophage densities were quantified from these images and analyzed with respect to the clinical presentations of the patients under investigation. RESULTS: A significantly greater macrophage density was found in unstable patients, both for fibrous and lipid-rich plaques (p = 0.025 and p = 0.002, respectively). Within each patient, the macrophage densities at culprit and non-culprit lesions correlated significantly (r = 0.66, y = 0.88x + 0.43, p = 0.01). Sites of plaque rupture demonstrated a greater macrophage density than non-ruptured sites (6.95 +/- 1.60%, 5.29 +/- 1.17%; p = 0.002). Surface macrophage infiltration was a stronger predictor of unstable clinical presentation than subsurface infiltration for culprit lesions (p = 0.035) but not for remote lesions (p = 0.80). CONCLUSIONS: Our results demonstrate that increases in both multi-focal and focal macrophage densities are highly correlated with symptom severity. By providing a means of detecting increases in plaque macrophage content before an acute event, this technique may aid in determining prognosis and guiding preventive therapy.

Aged↗

PubMed2004

Generating an adjustable three-dimensional dark focus.

Conditions for generating a dark focus surrounded by light in all three dimensions are presented. A simple technique for generating such a dark region is demonstrated experimentally. The method is compared with previous attempts at creating a three-dimensional dark focus.

Journal Article↗

PubMed2004

In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography.

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.

Humans↗

PubMed2004

Mechanical analysis of atherosclerotic plaques based on optical coherence tomography.

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.

Coronary Artery Disease↗