Adrien E. Desjardins

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.

Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging

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 (approximately 7-microm axial resolution, approximately 30-microm 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 3.0 to 7.0 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.

Removal of confounding effects of global signal in functional MRI analyses.

Local signals obtained from BOLD fMRI are generally confounded by global effects. In this paper, we make an essential distinction between global effects and the global signal. Global effects have a similar influence on local signals from a large proportion of cerebral voxels. They may reflect diffuse physiological processes or variations in scanner sensitivity and are difficult to measure directly. Global effects are often estimated from the global signal, which is the spatial average of local signals from all cerebral voxels. If the global signal is strongly correlated with experimental manipulations, meaningfully different results may be obtained whether or not global effects are modeled (G. K. Aguirre et al., 1998, NeuroImage, 8, 302-306). In particular, if local BOLD signals make a significant contribution to the global signal, analyses using ANCOVAor proportional scaling models may yield artifactual deactivations. In this paper, we present a modification to the proportional scaling model that accounts for the contribution of local BOLD signals to the global signal. An event-related oddball stimulus paradigm and a block design working memory task were used to illustrate the efficacy of our model.

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

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.

Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600 nm

We demonstrate a method to estimate the concentrations of water and lipid in scattering media such as biological tissues with diffuse optical spectra acquired over the range of 900 to 1600 nm. Estimations were performed by fitting the spectra to a model of light propagation in scattering media derived from diffusion theory. To validate the method, spectra were acquired from tissue phantoms consisting of lipid and water emulsions and swine tissues ex vivo with a two-fiber probe.

Estimation of biological chromophores using diffuse optical spectroscopy: Benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm

With an optical fiber probe, we acquired spectra from swine tissue between 500 and 1600 nm by combining a silicon and an InGaAs spectrometer. The concentrations of the biological chromophores were estimated by fitting a mathematical model derived from diffusion theory. The advantage of our technique relative to those presented in previous studies is that we extended the commonly-used wavelength ranges of 500 and 1000 nm to include the range of 1000 to 1600 nm, where additional water and lipid absorption features exist. Hence, a more accurate estimation of these two chromophores is expected when spectra are fitted between 500 and 1600 nm than between 500 and 1000 nm. When extending the UV-VIS wavelength range, the estimated total amount of chromophores approached 100% of the total as present in the probed volume. The confidence levels of the water and lipid related parameters increases by a factor of four.

Angle-resolved Optical Coherence Tomography with sequential angular selectivity for speckle reduction

We present a novel method for rapidly acquiring optical coherence tomography (OCT) images at multiple backscattering angles. By angularly compounding these images, high levels of speckle reduction were achieved. Signal-to-noise ratio (SNR) improvements of 3.4 dB were obtained from a homogeneous tissue phantom, which was in good agreement with the predictions of a statistical model of speckle that incorporated the optical parameters of the imaging system. In addition, the fast acquisition rate of the system (10 kHz A-line repetition rate) allowed angular compounding to be performed in vivo without significant motion artifacts. Speckle-reduced OCT images of human dermis show greatly improved delineation of tissue microstructure.

Increased ranging depth in optical frequency domain imaging by frequency encoding.

A technique for increasing the ranging depth in optical frequency domain imaging utilizing frequency encoding is presented. Ranging depth is enhanced by using two interferometer reference arms with different path lengths and independent modulation frequencies (25 and 50 MHz). With this configuration, the sensitivity decreases by 6 dB over a depth range of 7 mm, approximately a threefold improvement over the conventional optical frequency domain imaging technique. We demonstrate that the reference arm frequency separation, tuning speed, center wavelength, and instantaneous coherence length determine the signal-to-cross-talk ratio.

Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging

Speckle noise significantly limits the information content provided by coherent optical imaging methods such as optical coherence tomography and its recent derivative, optical frequency-domain imaging (OFDI). In this paper, we demonstrate a novel OFDI system that simultaneously acquires hundreds of angularly resolved images, which can be compounded to reduce speckle noise. The system comprises an InGaAs line-scan camera and an interferometer, configured so that the elements of the detector array simultaneously capture light spanning a backscattering angular range of 32 degrees. On successive read-outs of the array, the wavelength of the laser source was stepped through a range of 130 nm centered at 1295 nm to concurrently generate 400 angle-resolved OFDI images. A theory of angle-resolved OFDI and the design equations of the system are presented. Incoherent averaging of the angle-resolved data is shown to yield substantial speckle reduction (as high as an 8 dB SNR improvement) in images of a tissue phantom and esophageal tissue ex vivo.

Real-Time FPGA Processing for High-Speed Optical Frequency Domain Imaging

We present a novel algorithm for reconstructing interferograms acquired in optical frequency domain imaging (OFDI). The algorithm was developed specifically for processing in field programmable gate arrays (FPGAs) and featured the use of a finite-impulse-response (FIR) filter implementation of B-spline interpolation for efficiently re-sampling k-space. When implemented in FPGAs, the algorithm allowed for real-time processing of interferograms acquired with a high-speed OFDI system at 54 kHz and a sampling rate of 100 MS/s.