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1.  Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves 
Biomedical Optics Express  2014;5(12):4313-4328.
The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.
doi:10.1364/BOE.5.004313
PMCID: PMC4285607  PMID: 25574440
(110.4500) Optical coherence tomography; (240.6690) Surface waves; (280.3375) Laser induced ultrasonics
2.  In vivo imaging of functional microvasculature within tissue beds of oral and nasal cavities by swept-source optical coherence tomography with a forward/side-viewing probe 
Biomedical Optics Express  2014;5(8):2620-2634.
We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1300 nm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm × 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.
doi:10.1364/BOE.5.002620
PMCID: PMC4132993  PMID: 25136490
(170.4500) Optical coherence tomography; (170.2655) Functional monitoring and imaging; (170.1470) Blood or tissue constituent monitoring
3.  Laser induced surface acoustic wave combined with phase sensitive optical coherence tomography for superficial tissue characterization: a solution for practical application 
Biomedical Optics Express  2014;5(5):1403-1419.
Mechanical properties are important parameters that can be used to assess the physiologic conditions of biologic tissue. Measurements and mapping of tissue mechanical properties can aid in the diagnosis, characterisation and treatment of diseases. As a non-invasive, non-destructive and non-contact method, laser induced surface acoustic waves (SAWs) have potential to accurately characterise tissue elastic properties. However, challenge still exists when the laser is directly applied to the tissue because of potential heat generation due to laser energy deposition. This paper focuses on the thermal effect of the laser induced SAW on the tissue target and provides an alternate solution to facilitate its application in clinic environment. The solution proposed is to apply a thin agar membrane as surface shield to protect the tissue. Transient thermal analysis is developed and verified by experiments to study the effects of the high energy Nd:YAG laser pulse on the surface shield. The approach is then verified by measuring the mechanical property of skin in a Thiel mouse model. The results demonstrate a useful step toward the practical application of laser induced SAW method for measuring real elasticity of normal and diseased tissues in dermatology and other surface epithelia.
doi:10.1364/BOE.5.001403
PMCID: PMC4026889  PMID: 24877004
(240.6690) Surface waves; (280.3375) Laser induced ultrasonics; (350.5030) Phase
4.  Pulsatile motion of the trabecular meshwork in healthy human subjects quantified by phase-sensitive optical coherence tomography 
Biomedical Optics Express  2013;4(10):2051-2065.
Aqueous leaves the anterior chamber of eye by passing through the trabecular meshwork (TM), a tissue thought to be responsible for increased outflow resistance in glaucoma. Motion assessment could permit characterization of TM biomechanical properties necessary to maintain intra-ocular pressure (IOP) within a narrow homeostatic range. In this paper, we report the first in vivo identification of TM motion in humans. We use a phase-sensitive optical coherence tomography (PhS-OCT) system with sub-nanometer sensitivity to detect and image dynamic pulse-induced TM motion. To permit quantification of TM motion and relationships we develop and apply a phase compensation algorithm permitting removal of the otherwise evitable confounding effects of bulk motion. Twenty healthy human eyes from 10 subjects are imaged. The results permit visualization of pulsatile TM motion visualization by PhS-OCT; correlation with the digital/cardiac pulse is highly significant. The correlation permits assessment of the phase lag and time delay between TM motion and the cardiac pulse. In this study, we find that the digital pulse leads the pulsatile TM motion by a mean phase of 3.53 ± 0.48 rad and a mean time of 0.5 ± 0.14 s in the fundamental frequency. A significant linear relationship is present between the TM phase lag and the heart rate (p value < 0.05). The TM phase lag is also affected by age, the relationship not quite reaching significance in the current study. PhS-OCT reveals pulse-induced motion of the TM that may provide insights into the biomechanics of the tissues involved in the regulation of IOP.
doi:10.1364/BOE.4.002051
PMCID: PMC3799665  PMID: 24156063
(170.4500) Optical coherence tomography; (170.0110) Imaging systems; (170.3880) Medical and biological imaging; (170.4470) Ophthalmology
5.  Super-resolution spectral estimation of optical micro-angiography for quantifying blood flow within microcirculatory tissue beds in vivo 
Biomedical Optics Express  2013;4(7):1214-1228.
In this paper, we propose a super-resolution spectral estimation technique to quantify microvascular hemodynamics using optical microangiography (OMAG) based on optical coherence tomography (OCT). The proposed OMAG technique uses both amplitude and phase information of the OCT signals which makes it sensitive to the axial and transverse flows. The scanning protocol for the proposed method is identical to three-dimensional ultrahigh sensitive OMAG, and is applicable for in vivo measurements. In contrast to the existing capillary flow quantification methods, the proposed method is less sensitive to tissue motion and does not have aliasing problems due fast flow within large blood vessels. This method is analogous to power Doppler in ultrasonography and estimates the number of red blood cells passing through the beam as opposed to the velocity of the particles. The technique is tested both qualitatively and quantitatively by using OMAG to image microcirculation within mouse ear flap in vivo.
doi:10.1364/BOE.4.001214
PMCID: PMC3704100  PMID: 23847744
(170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography
6.  High-resolution 1050 nm spectral domain retinal optical coherence tomography at 120 kHz A-scan rate with 6.1 mm imaging depth 
Biomedical Optics Express  2013;4(2):245-259.
We report a newly developed high speed 1050nm spectral domain optical coherence tomography (SD-OCT) system for imaging posterior segment of human eye. The system is capable of an axial resolution at ~10 µm in air, an imaging depth of 6.1 mm in air, a system sensitivity fall-off at ~6 dB/3mm and an imaging speed of 120,000 A-scans per second. We experimentally demonstrate the system’s capability to perform phase-resolved imaging of dynamic blood flow within retina, indicating high phase stability of the SDOCT system. Finally, we show an example that uses this newly developed system to image posterior segment of human eye with a large view of view (10 × 9 mm2), providing detailed visualization of microstructural features from anterior retina to posterior choroid. The demonstrated system parameters and imaging performances are comparable to those that a typical 1 µm swept source OCT would deliver for retinal imaging.
doi:10.1364/BOE.4.000245
PMCID: PMC3567712  PMID: 23411636
(170.4460) Ophthalmic optics and devices; (170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography
7.  Digital focusing of OCT images based on scalar diffraction theory and information entropy 
Biomedical Optics Express  2012;3(11):2774-2783.
This paper describes a digital method that is capable of automatically focusing optical coherence tomography (OCT) en face images without prior knowledge of the point spread function of the imaging system. The method utilizes a scalar diffraction model to simulate wave propagation from out-of-focus scatter to the focal plane, from which the propagation distance between the out-of-focus plane and the focal plane is determined automatically via an image-definition-evaluation criterion based on information entropy theory. By use of the proposed approach, we demonstrate that the lateral resolution close to that at the focal plane can be recovered from the imaging planes outside the depth of field region with minimal loss of resolution. Fresh onion tissues and mouse fat tissues are used in the experiments to show the performance of the proposed method.
doi:10.1364/BOE.3.002774
PMCID: PMC3493221  PMID: 23162717
(170.4500) Optical coherence tomography; (100.1830) Deconvolution; (100.6950) Tomographic image processing; (100.3190) Inverse problems; (110.3000) Image quality assessment
8.  Impact of intraocular pressure on changes of blood flow in the retina, choroid, and optic nerve head in rats investigated by optical microangiography 
Biomedical Optics Express  2012;3(9):2220-2233.
In this paper, we demonstrate the use of optical coherence tomography/optical microangiography (OCT/OMAG) to image and measure the effects of acute intraocular pressure (IOP) elevation on retinal, choroidal and optic nerve head (ONH) perfusion in the rat eye. In the experiments, IOP was elevated from 10 to 100 mmHg in 10 mmHg increments. At each IOP level, three-dimensional data volumes were captured using an ultrahigh sensitive (UHS) OMAG scanning protocol for 3D volumetric perfusion imaging, followed by repeated B-scans for Doppler OMAG analysis to determine blood flow velocity. Velocity and vessel diameter measurements were used to calculate blood flow in selected retinal blood vessels. Choroidal perfusion was calculated by determining the peripapillary choroidal filling at each pressure level and calculating this as a percentage of area filling at baseline (10 mmHg). ONH blood perfusion was calculated as the percentage of blood flow area over a segmented ONH area to a depth 150 microns posterior to the choroidal opening. We show that volumetric blood flow reconstructions revealed detailed 3D maps, to the capillary level, of the retinal, choroidal and ONH microvasculature, revealing retinal arterioles, capillaries and veins, the choroidal opening and a consistent presence of the central retinal artery inferior to the ONH. While OCT structural images revealed a reversible compression of the ONH and vasculature with elevated IOP, OMAG successfully documented changes in retinal, choroidal and ONH blood perfusion and allowed quantitative measurements of these changes. Starting from 30 mm Hg, retinal blood flow (RBF) diminished linearly with increasing IOP and was nearly extinguished at 100 mm Hg, with full recovery after return of IOP to baseline. Choroidal filling was unaffected until IOP reached 60 mmHg, then decreased to 20% of baseline at IOP 100 mmHg, and normalized when IOP returned to baseline. A reduction in ONH blood perfusion at higher IOP’s was also observed, but shadow from overlying retinal vessels at lower IOP’s limited precise measurements of changes in ONH capillary perfusion compared to baseline. Therefore, OCT/OMAG can be a useful tool to image and measure blood flow in the retina, choroidal and ONH of the rat eye as well as document the effects of elevated IOP on blood flow in these vascular beds.
doi:10.1364/BOE.3.002220
PMCID: PMC3447563  PMID: 23024915
(170.4460) Ophthalmic optics and devices; (170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography
9.  Introduction: feature issue on In Vivo Microcirculation Imaging 
Biomedical Optics Express  2011;2(7):1861-1863.
The editors introduce the Biomedical Optics Express feature issue, “In Vivo Microcirculation Imaging,” which includes 14 contributions from the biomedical optics community, covering such imaging techniques as optical coherence tomography, photoacoustic microscopy, laser Doppler /speckle imaging, and near infrared spectroscopy and fluorescence imaging.
doi:10.1364/BOE.2.001861
PMCID: PMC3130573  PMID: 21750764
(000.1200) Announcements, awards, news, and organizational activities; (170.3880) Medical and biological imaging; (170.4500) Optical coherence tomography; (110.5120) Photoacoustic imaging; (110.1080) Active or adaptive optics; (170.4580) Optical diagnostics for medicine
10.  Highly sensitive imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography 
Biomedical Optics Express  2011;2(5):1059-1068.
Studying renal microcirculation and its dynamics is of great importance for understanding the renal function and further aiding the diagnosis, prevention and treatment of renal pathologies. In this paper, we present a potentially useful method to provide high-sensitive volumetric imaging of renal microcirculations using ultrahigh-sensitive optical microangiography (UHS-OMAG). The UHS-OMAG image system used here is based on spectral domain optical coherence tomography, which uses a broadband light source centered at 1300 nm with an imaging speed of 150 frames per second that requires ~6.7 sec to complete one 3D scan of ~2.5 × 2.5 mm2 area. The technique is sensitive enough to image capillary networks, such as peritubular capillaries within renal cortex. We show the ability of UHS-OMAG to provide depth-resolved volumetric images of capillary level renal microcirculation. We also show that UHS-OMAG is capable of monitoring the changes of renal microcirculation in response to renal ischemia and reperfusion. Finally, we attempt to show the capability of OMAG to provide quantitative analysis about velocity changes in a single capillary vessel (down to tens of microns per second) in response to the ischemic event.
doi:10.1364/BOE.2.001059
PMCID: PMC3087564  PMID: 21559119
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging
11.  Measurement of absolute blood flow velocity in outflow tract of HH18 chicken embryo based on 4D reconstruction using spectral domain optical coherence tomography 
Biomedical optics express  2010;1(3):798-811.
The measurement of blood-plasma absolute velocity distributions with high spatial and temporal resolution in vivo is important for the investigation of embryonic heart at its early stage of development. We introduce a novel method to measure absolute blood flow velocity based on high speed spectral domain optical coherence tomography (OCT) and apply it to measure velocities across the heart outflow tract (OFT) of a chicken embryo (stage HH18). First, we use the OCT system to acquire 4D [(x,y,z) + t] images of the OFT in vivo. Second, we reconstruct the 4D microstructural images and obtain the orientation of the OFT at its maximum expansion, from which the centerline of the OFT is calculated based on the OFT boundary segmentation. Assuming flow is parallel to the vessel orientation, the obtained centerline indicates the flow direction. Finally, the absolute flow velocity is evaluated based on the direction given by the centerline and the axial velocity obtained from Doppler OCT. Using this method, we compare flow velocity profiles at various positions along the chicken embryo OFT.
doi:10.1364/BOE.1.000798
PMCID: PMC2994554  PMID: 21127734
12.  Measurement of absolute blood flow velocity in outflow tract of HH18 chicken embryo based on 4D reconstruction using spectral domain optical coherence tomography 
Biomedical Optics Express  2010;1(3):798-811.
The measurement of blood-plasma absolute velocity distributions with high spatial and temporal resolution in vivo is important for the investigation of embryonic heart at its early stage of development. We introduce a novel method to measure absolute blood flow velocity based on high speed spectral domain optical coherence tomography (OCT) and apply it to measure velocities across the heart outflow tract (OFT) of a chicken embryo (stage HH18). First, we use the OCT system to acquire 4D 
[(x,y,z) + t] images of the OFT in vivo. Second, we reconstruct the 4D microstructural images and obtain the orientation of the OFT at its maximum expansion, from which the centerline of the OFT is calculated based on the OFT boundary segmentation. Assuming flow is parallel to the vessel orientation, the obtained centerline indicates the flow direction. Finally, the absolute flow velocity is evaluated based on the direction given by the centerline and the axial velocity obtained from Doppler OCT. Using this method, we compare flow velocity profiles at various positions along the chicken embryo OFT.
doi:10.1364/BOE.1.000798
PMCID: PMC2994554  PMID: 21127734
(170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging; (110.4155) Multiframe image processing

Results 1-12 (12)