KEYWORDS: Optical coherence tomography, Luminescence, Imaging systems, Tissues, Process control, Near infrared, Visualization, Standards development, Lens design, Control systems
We present our next generation clinical dual-modality OCT and near infrared autofluorescence/fluorescence (NIRAF/NIRF) imaging platform. This platform allows combined tissue microstructure visualization (OCT) and obtaining molecular information either by intrinsic tissue near infrared autofluorescence (NIRAF) or by exogenous near infrared fluorescence contrast agents (NIRF). Components of this platform, OCT-NIRAF/NIRF imaging system, rotary junction and catheters, were developed using an industry standard design control processes to enable quality clinical translation. We have identified sources of image degradation in dual-modality catheter-based imaging (e.g. core-cladding crosstalk in OCT, background noise in fluorescence) and present methods to mitigate their effects. We also show catheter fabrication and validation, as well as automated fluorescence sensitivity and distance calibration methods that ensure robust and repeatable system performance.
Laser pulses in either laboratory or industry are typically complex objects. Unlike the classical electro-magnetic wave with uniform polarization distribution along the flat wave-front or a general vector beam under the paraxial approximation, the real light pulses, such as the pulses from the high power multimode fiber laser and the dechirped femtosecond pulses with structured wave-front, spectrum and polarization distributions, usually have non-vanishing component in the propagation direction. Therefore, the description of a general vectorial laser pulse should be implemented in multi-dimensional way, for the light is the combination of a three-dimensional(3D) vector field (electric field E) and a 3D pseudovector field (magnetic field B) in the 3D Euclidean space (R3). Here we report on a novel technique for the multi-dimensional characterization which includes the spatiotemporal amplitude and phase information as well as the vectorial features in 3D Euclidean space of the complex laser pulses, such as the intrinsically controlled femtosecond pulses with higher-order Poincaré sphere beams and vectoral spherical beams. A two-steps-based polarization-sensitive Mach–Zehnder interferometer temporal scan technique was used, at the first time, to capture the complete information of the pulses. The corresponding measurement device, placed on the collimated and attenuated beam at the laser output is consists of a special Mach–Zehnder interferometer, a polarizing beam-splitter and charge-coupled device (CCD) cameras. The reference beam with vertical and horizontal polarization is exported from the cavity and attenuated to a suitable intensity by using a neutral-density filter. After 3D phase unwrapping, removal of the reference curvature, correction of achromatic wave-front distortions, spectral phase and amplitude reconstructions, as well as the measurement for the intrinsic phase of the reference pulse, the complete information of the pulse, include the phase information of the three electronic components, will be obtained. This new measurement capability opens the way to in-depth characterizations and optimizations of the complex laser pulses and ultimately to the study of new phenomena of multimode fiber laser generated laser pulse as well as the interactions between materials and structured ultra-short laser beams.
Coronary arteries are covered by a thin layer of endothelial cells (ECs). Impairment of ECs is at the origin of coronary atherosclerosis and its clinical manifestations. However, the study of ECs in humans remains elusive because of a lack of an imaging tool with sufficient resolution. We have developed a light-based 1-µm-resolution microscopic imaging technology termed micro-optical coherence tomography (µOCT) that can be implemented in a coronary catheter. In this study, we investigated the capability of µOCT to visualize EC morphology. We stripped the endothelium from 36 fresh swine coronary segments with cyanoacrylate glue. Histology showed that the stripping procedure successfully removed ECs from the swine coronary arteries. Coronary segments were then imaged in 3D with µOCT, and were processed for histology and scanning electron microscopy (SEM). µOCT images of stripped vs. intact sites were volume rendered in 3D and visually compared. 3D-µOCT allowed visualization of EC pavementing on intact artery surfaces that was strongly correlated to that seen by SEM. EC pavementing disappeared, and surface roughness calculated by computed root mean squared error diminished significantly at the sites with stripped EC compared with intact sites. µOCT was also utilized in human cadaver coronary arteries, showing its capability of identifying EC morphology of human coronary plaque harboring leukocyte adhesion, EC stent strut tissue coverage, and lack of ECs at lesions with necrotic core or superficial nodular calcifications. In conclusion, µOCT enables EC visualization in coronary arteries, suggesting that it could be useful in patients with coronary artery disease to better understand the role of ECs in the pathogenesis of coronary artery disease.
Light carries both spin and orbital angular momentum and the superpositions of these two dynamical properties have found many applications. Many techniques exist to create such light sources but none allow their creation at the femtosecond laser. Here we report on a novel mode-locked ytterbium-doped fiber laser that generates femtosecond pulses with higher-order Poincaré sphere beams. The controlled generation of such pulses such as azimuthally and radially polarized light with definite orbital angular momentum modes are demonstrated. A unidirectional ring cavity constructed with the Yb-doped fiber placed at the end of the fiber section to reduces unnecessary nonlinear effects is employed for self-starting operation. Two pairs of diffraction gratings are used for compensating the normal group velocity dispersion of the fiber and other elements. Mode-locked operation is achieved based on nonlinear polarization evolution, which is mainly implemented with the single mode fiber, the bulk wave plates and the variable spiral plates (q-plate with topological charge q=0.5). The conversion from spin angular momentum to the OAM and reverse inside the laser cavity are realized by means of a quarter-wave plate and a q-plate so that the polarization control was mapped to OAM mode control.
To demonstrate the total spatiotemporal and vectoral characterization of the new type femtosecond laser beams, here, a polarization-sensitive Mach–Zehnder interferometer temporal scan technique was used, at the first time, to capture the complete information of the pulse. The corresponding measurement device, placed on the collimated and attenuated beam at the laser output and simply consists of a special Mach–Zehnder interferometer, a polarizing beam-splitter and two charge-coupled device (CCD) cameras. The reference beam with vertical polarization is exported from the cavity and attenuated to a suitable intensity by using a neutral-density filter. After Fourier filtering, removal of the reference curvature, correction of achromatic wave-front distortions, spectral phase and amplitude reconstructions, as well as the measurement for the intrinsic phase of the reference pulse, the complete information of the pulse will be obtained. This new measurement capability opens the way to in-depth characterization and optimization of the vector vortex femtosecond laser pulse and ultimately to the detection of new phenomena of the interactions between materials and structured femtosecond laser beams in space–time and polarization.
Optical coherence tomography (OCT) has been a useful clinical tool for diagnosing coronary artery disease through a flexible catheter, but its full promise relies on resolving cellular and sub-cellular structures in vivo. Previously, visualizing cellular structures through an imaging catheter is not possible due to limited depth of focus (DOF) of a tightly focused Gaussian beam: typically, a Gaussian beam with 2-3 μm resolution has a DOF within 100 μm, which is not sufficient for in vivo catheter imaging. Therefore, we developed a self-imaging wavefront division optical system that generates a coaxially-focused multimode (CAFM) beam with a DOF that is approximately one order of magnitude longer than that of a Gaussian beam. In this study, we present a high-resolution, extended DOF catheter based on self-imaging wavefront division optics. The catheter generates a CAFM beam with a lateral resolution of 3 μm and a DOF close to 2 mm. To correct the aberration introduced by catheter sheath, we incorporated a cylindrical prism to compensate the sheath astigmatism. When the catheter is incorporated into a micro-resolution OCT (μOCT) system with rotational scanning mechanics, cellular-resolution cross-sectional images of the coronary artery wall can be obtained. The device serves as an important step toward characterizing cellular and sub-cellular structures in vivo for coronary artery disease diagnosis.
Acute cardiovascular events are mostly due to a blood clot or thrombus induced by the sudden rupture of vulnerable atherosclerotic plaques within coronary artery walls. Based on the high optical absorption contrast of the lipid rich plaques within the vessel wall, intravascular photoacoustic (IVPA) imaging at 1.7 μm spectral band has shown promising capabilities for detecting of lipid composition, but the translation of the technology for in vivo application is limited by the slow imaging speed. In this work, we will present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm (5 nm linewidth). A miniature catheter with 1.0 mm outer diameter was designed with a polished 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. Two optical illumination methods by gradient-index (GRIN) lens and ball lens are introduced and compared for higher spatial resolution. At 1725 nm, atherosclerotic rabbit abdominal aorta was imaged at two frame per second, which is more than one order of magnitude faster than previous reported IVPA imaging. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo.
Changes in tissue biomechanical properties often signify the onset and progression of diseases, such as in determining the vulnerability of atherosclerotic plaques. Acoustic radiation force optical coherence elastography (ARF-OCE) has been used in the detection of tissue elasticity to obtain high-resolution elasticity maps. We have developed a probe-based ARF-OCE technology that utilizes a miniature 10 MHz ring ultrasonic transducer for excitation and Doppler optical coherence tomography (OCT) for detection. The transducer has a small hole in the center for the OCT light to propagate through. This allows for a confocal stress field and light detection within a small region for high sensitivity and localized excitation. This device is a front-facing probe that is only 3.5 mm in diameter and it is the smallest ARF-OCE catheter to the best of our knowledge. We have tested the feasibility of the probe by measuring the point displacement of an agarose tissue-mimicking phantom using different ARF excitation voltages. Small displacement values ranging from 30 nm to 90 nm have been detected and are shown to be directly proportional to the excitation voltage as expected. We are currently working on obtaining 2D images using a scanning mechanism. We will be testing to capture 2D elastograms of phantoms to further verify feasibility, and eventually characterize the mechanical properties of cardiovascular tissue. With its high portability and sensitivity, this novel technology can be applied to the diagnosis and characterization of vulnerable atherosclerotic plaques.
Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.
Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging technique for microvasculature imaging at high spatial resolution and contrast. In this work, we present a practical visible laser-diode-based OR-PAM (LD-OR-PAM) prototype for vasculature imaging, which has the desirable properties of being portable, low-cost, and label-free. The prototype employs a 300 mW pulsed laser diode in a 3.8 mm diameter package, emitting 174 ns pulses at 405 ± 5 nm wavelength and a pulse energy of 52 nJ. An aspheric objective with a numerical aperture of 0.60 is used to achieve microscope optical illumination. The laser diode excitation has a compact size of 4.5 × 1.8 × 1.8 cm3 assembled with a cooling block. The lateral resolution was tested to be 0.95 μm on ~7 μm carbon fibers. The subcutaneous microvasculature on a mouse back was label-free imaged ex vivo, which demonstrates the potential of the LD-OR-PAM prototype for in vivo imaging skin chromosphores such as hemoglobin. Our ultimate aim is to provide a practical and affordable OR-PAM system as a routine instrument for standard clinical applications.
Optical coherence tomography (OCT) is a noninvasive method for retinal imaging. In this work, we present an in vivo
human retinal microvascular network measurement by an intensity-based Doppler variance (IBDV) based on sweptsource
OCT. In addition, an automatic three-dimensional (3-D) segmentation method was used for segmenting
intraretinal layers. The microvascular networks were divided into six layers by visualizing of each individual layer with
enhanced imaging contrast. This method has potential for earlier diagnosis and precise monitoring in retinal vascular
diseases.
Microvascular network of the retina plays an important role in diagnosis and monitoring of various retinal diseases. We propose a three-dimensional (3-D) segmentation method with intensity-based Doppler variance (IBDV) based on swept-source optical coherence tomography. The automatic 3-D segmentation method is used to obtain seven surfaces of intraretinal layers. The microvascular network of the retina, which is acquired by the IBDV method, can be divided into six layers. The microvascular network of the six individual layers is visualized, and the morphology and contrast images can be improved by using the segmentation method. This method has potential for earlier diagnosis and precise monitoring in retinal vascular diseases.
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