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Biomedical subjects

Zhongping Chen

Publications and source records attributed to Zhongping Chen.

At least 19 recordsLinked to original sources

Fiber-optic-bundle-based optical coherence tomography.

A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.

Animals↗

Ultrahigh-resolution optical coherence tomography with a fiber laser source at 1 microm.

We report a compact, high-power, fiber-based source for ultrahigh-resolution optical coherence tomography (OCT) near 1 microm. The practical source is based on a short-pulse, ytterbium-doped fiber laser and on generation of a continuum spectrum in a photonic crystal fiber. The broadband emission has an average power of 140 mW and offers an axial resolution of 2.1 microm in air (<1.6 microm in biological tissue). The generation of a broad bandwidth is robust and efficient. We demonstrate ultrahigh-resolution, time-domain OCT imaging of in vitro and in vivo biological tissues.

Equipment Design↗

Low-voltage polymer-based scanning cantilever for in vivo optical coherence tomography.

Novel hand-held optical coherence tomography (OCT) probes with polymer cantilevers have been developed for clinical oral and skin imaging. An electroactive ionic polymer-metal composite cantilever was used to generate 3-mm transverse scanning movement of an optical fiber with applied 2-V linear alternating voltage at 1 Hz. Low driving voltage ensures safety. Two different optical designs achieve both forward and sidewise scanning and make it possible to image everywhere within the human oral cavity. In vivo OCT imaging of the human tongue is demonstrated.

Equipment Design↗

Characterization of submucosal lesions using optical coherence tomography in the rabbit subglottis.

OBJECTIVE: To evaluate the efficacy of optical coherence tomography in differentiating between several simulated subglottic lesions, using an ex vivo rabbit laryngotracheal model. DESIGN: Laryngotracheal complexes were harvested from euthanized rabbits and divided into the following 4 groups: (1) control, (2) submucosal collagen injection (simulating scar formation), (3) dehydration and rehydration (simulating edema), and (4) repeated intubation trauma. The subglottic region was imaged using optical coherence tomography. Images were later correlated with conventional histologic findings. RESULTS: The epithelium, basement membrane, lamina propria, perichondrium, and cartilage (cricoid and tracheal) were clearly imaged. In group 2, an increase in the thickness of the lamina propria was observed, in addition to a characteristic optical pattern of the injected collagen. Dehydration (in group 3) produced a visible reduction in the thickness of the lamina propria, while rehydration of the same specimen with distilled water revealed a significant increase in submucosal swelling. Repeated intubation (in group 4) resulted in tissue edema that was seen as wavy heterogeneous thickening of the lamina propria. Edema produced by repeated intubation or distilled water immersion was easily differentiated from native and collagen-injected tissues. CONCLUSION: Optical coherence tomography successfully identifies the microstructure layers of the subglottis and can differentiate between edema and increased collagen deposition in the rabbit model.

Animals↗

In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients.

OBJECTIVES: Optical coherence tomography (OCT) is an emerging imaging modality that combines low-coherence light with interferometry to produce cross-sectional images of tissue with resolution about 10 mum. Patients undergoing surgical head and neck endoscopy were examined using a fiberoptic OCT imaging probe to study and characterize microstructural anatomy and features of the larynx and benign laryngeal pathology in vivo. STUDY DESIGN: Prospective clinical trial. MATERIALS AND METHODS: OCT imaging of the larynx was performed in 82 of 115 patients who underwent surgical endoscopy for various head and neck pathologies. The OCT device employs a 1.3 microm broadband light source (FWHM, 80 nm). The frame rate is 1 Hz. Imaging was performed using a handheld probe placed in near contact with the target site. The maximum axial and lateral dimensions for the region of interest imaged were 2.5 mm x 6 mm, with resolutions of 10 microm. Simultaneously, conventional endoscopic images were obtained to provide anatomic correlation with OCT images and histology. Optical micrometry was performed to measure the epithelium thickness. RESULTS: Systematic OCT imaging of laryngeal structures and subsites provided information on the thickness of the epithelium, integrity of the basement membrane, and structure of the lamina propria. Microstructural features identified included glands, ducts, blood vessels, fluid collection/edema, and the transitions between pseudostratified columnar and stratified squamous epithelium. The mean epithelial thickness of laryngeal subsites was calculated: true vocal cord (129 microm), false vocal cords (124 microm), aryepiglottic fold (177 microm), subglottis (98 microm), and epiglottis (185 microm). True vocal cord pathology imaged included Reinke's edema, papillomatosis, polyps, mucous cysts, and granulation tissue. Subglottic imaging identified boundaries between epithelium, lamina propria, and cartilage. The OCT images compared favorably with conventional histopathology. CONCLUSION: OCT has the unique ability to image laryngeal tissue microstructure and can detail microanatomic changes in benign, premalignant, and malignant laryngeal pathologies. OCT holds the potential to guide surgical biopsies, direct therapy, and monitor disease, particularly when office-based systems are developed. This is a promising imaging modality to study the larynx.

Biopsy↗

Low-noise broadband light generation from optical fibers for use in high-resolution optical coherence tomography.

Broadband light generation from a single-mode optical fiber was developed for high-resolution optical coherence tomography (OCT). No noise amplification was observed for light broadened by self-phase modulation. The investigation showed that the intensity noise of light broadened by self-phase modulation in a single-mode optical fiber was much lower than that of continuum light from a microstructure fiber (MSF). The spectral width of a femtosecond input laser pulse was successfully broadened by a factor of 11, and a coherence length of 3.7 microm was achieved with this source. The application of light broadened by a single-mode optical fiber and MSF was compared for use in OCT imaging. The results showed that a single-mode fiber with a small core diameter is a useful way to generate low-noise, broadband light for high-resolution OCT imaging.

Algorithms↗

Depth-resolved birefringence and differential optical axis orientation measurements with fiber-based polarization-sensitive optical coherence tomography.

Conventional polarization-sensitive optical coherence tomography (PS-OCT) can provide depth-resolved Stokes parameter measurements of light reflected from turbid media. A new algorithm that takes into account changes in the optical axis is introduced to provide depth-resolved birefringence and differential optical axis orientation images by use of fiber-based PS-OCT. Quaternion, a convenient mathematical tool, is used to represent an optical element and simplify the algorithm. Experimental results with beef tendon and rabbit tendon and muscle show that this technique has promising potential for imaging the birefringent structure of multiple-layer samples with varying optical axes.

Algorithms↗

In vivo endoscopic optical coherence tomography by use of a rotational microelectromechanical system probe.

A novel endoscopic optical coherence tomography probe was designed and constructed with a 1.9-mm microelectromechanical system (MEMS) motor. The new MEMS endoscopic probe design eliminates the need to couple the rotational energy from the proximal to the distal end of the probe. Furthermore, the endoscopic probe's sheath and fiber have the advantages of having a much smaller diameter and being more flexible than traditional endoscopes since no reinforcement is needed to couple the rotational torque. At the distal end, a prism mounted on a micromotor deflects the light rays to create a transverse circular-scanning pathway. Because our MEMS scanner does not require the coupling of a rotational single-mode fiber, a high scanning speed is possible while eliminating unstable optical signals caused by nonuniform coupling.

Anatomy, Cross-Sectional↗

Second-harmonic optical coherence tomography.

Second-harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical responses of biological tissues for imaging, is described and demonstrated. Femtosecond laser pulses were used to excite second-harmonic waves from collagen harvested from rat tail tendon and a reference non-linear crystal. Second-harmonic interference fringe signals were detected and used for image construction. Because of the strong dependence of second-harmonic generation on molecular and tissue structures, this technique imparts contrast and resolution enhancement to conventional optical coherence tomography.

Animals↗

Feasibility study of normal and septic tracheal imaging using optical coherence tomography.

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) is an imaging technology that may be adapted for use with flexible fiberoptic bronchoscopy, potentially allowing it to play an important role in pulmonary diagnostics. The goal of this study was to evaluate the feasibility of OCT to image tracheal pathology. STUDY DESIGN/MATERIALS AND METHODS: Tracheas were harvested from normal and septic New Zealand White rabbits and imaged using OCT. Two delivery devices were employed. One was a moving stage with an objective lens and collimator, the other a linear scanning flexible fiberoptic catheter using a GRIN lens and prism for endoscopic OCT. After OCT images were obtained from normal and septic tracheas, the excised tissues were prepared for standard histologic examination. Areas imaged by OCT were compared with corresponding histology slides. RESULTS: OCT images demonstrated in detail tracheal sub-surface structures such as the epithelium, lamina propria, submucosa, and cartilage. The appearance of structures imaged by OCT corresponded very well with histologic pictures obtained by light microscopy. The OCT images from septic tracheas showed marked swelling of the mucosal and submucosal layers. Such pathology was equally imaged by either the moving stage or fiberoptic catheter for endoscopic OCT. CONCLUSIONS: OCT images of the trachea can distinguish many sub-surface structural features usually requiring biopsy and light microscopy for visualization. Marked differences between normal and septic trachea were apparent in OCT images. In the future, OCT may be a valuable tool for evaluating tracheal pathology in situ with high image resolution.

Animals↗

In vivo optical coherence tomography for the diagnosis of oral malignancy.

BACKGROUND AND OBJECTIVE: Oral cancer results in 10,000 U.S. deaths annually. Improved highly sensitive diagnostics allowing early detection of oral cancer would benefit patient survival and quality of life. Objective was to investigate in vivo non-invasive optical coherence tomography (OCT) techniques for imaging and diagnosing neoplasia-related epithelial, sub-epithelial changes throughout carcinogenesis. STUDY DESIGN/MATERIALS AND METHODS: In the standard hamster cheek pouch model for oral carcinogenesis (n = 36), in vivo OCT was used to image epithelial and sub-epithelial change. OCT- and histopathology-based diagnoses on a scale of 0 (healthy) to 6 (squamous cell carcinoma, SCC) were performed at all stages throughout carcinogenesis by two blinded investigators. RESULTS: Epithelial, sub-epithelial structures were clearly discernible using OCT. OCT diagnosis agreed with the histopathological gold standard in 80% of readings. CONCLUSION: In vivo OCT demonstrates excellent potential as a diagnostic tool in the oral cavity.

Animals↗

Imaging the internal structure of the rat cochlea using optical coherence tomography at 0.827 microm and 1.3 microm.

OBJECTIVE: The purpose of this study was to use high-speed optical coherence tomography (OCT) to obtain cross-sectional images of the rat cochlea. STUDY DESIGN AND METHODS: The cochleae of Sprague- Dawley rats were imaged within 2 to 4 hours after death. Specimens were prepared by removing the bulla to expose the mesotympanum; some images were obtained in intact temporal bones removed from the cranium. The central element of an OCT imaging device is a Michelson interferometer combined with a low-coherence light source. This study used 2 OCT systems with different light sources: 1) a semiconductor optical amplifier operating and 2) a superluminescent diode with peak emissions wavelengths of 1.3 microm and 827 nm, respectively. Images (1.87 x 2.00 mm or 1.87 x 1.00 mm, 10 x 10 microm pixel resolution) were acquired at a frame rate of 1 Hz. Cross-sectional images at 100-microm increments were obtained from a medial-to-lateral direction. RESULTS: The scala vestibuli, scala media, scala tympani, modiolus, spiral ligament, and several turns of the cochlea were identified. CONCLUSION: These images reflect the ability of OCT to provide images of the internal cochlea structure with micron scale resolution and at near-real time frame rates.

Anatomy, Cross-Sectional↗

Dynamic morphology of sutureless cataract wounds--effect of incision angle and location.

OBJECTIVE: Sutureless cataract surgery has been growing in popularity over the last decade. These clear corneal incisions allow for rapid visual recovery after phacoemulsification, but may be associated with an increased risk of endophthalmitis. The purpose of this study was to evaluate the effect of intraocular pressure (IOP), location, and angle of cataract incisions on wound apposition and sealing in postmortem globes. METHODS: This was an ex vivo laboratory investigation of 20 rabbit eyes and 14 human eyes. Self-sealing clear corneal, limbal, and scleral incisions were created and IOP was controlled with an infusion cannula. Incisions were made at a variety of angles. Optical coherence tomography was used to image the incisions in real time as the IOP was varied by raising and lowering the infusion bottle, so as to simulate the variation in IOP occurring with blinking or squeezing of the eye. RESULTS: With each type of incision, optical coherence tomography demonstrated the dynamic nature of cataract wound morphology as IOP was varied. Higher IOPs, in general, were associated with more tightly sealed wounds than lower IOPs, but this varied according to the location and angle of the incisions. More perpendicular incisions, relative to the surface tangent, sealed less well than incisions created at smaller angles at higher levels of IOP; At lower IOPs, the reverse relationship was observed such that more perpendicular incisions sealed less well than smaller incision angles. CONCLUSION: Changes in IOP may result in variable and sometime poor wound apposition in sutureless cataract incisions. The type of incision and angle of the incision may affect the likelihood of inoculation of the aqueous humor with potentially pathogenic bacteria. For each type of incision, there may be a critical angle at which the incision is better able to withstand fluctuations in IOP.

Animals↗

Ultrahigh-resolution optical coherence tomography by broadband continuum generation from a photonic crystal fiber.

We have developed an ultrahigh-resolution optical coherence tomographic system in which broadband continuum generation from a photonic crystal fiber is used to produce high longitudinal resolution. Longitudinal resolution of 1.3-microm has been achieved in a biological tissue by use of continuum light from 800 to 1400 nm. The system employed a dynamic-focusing tracking method to maintain high lateral resolution over a large imaging depth. Subcellular imaging is demonstrated.

Animals↗

Dynamic morphology of clear corneal cataract incisions.

OBJECTIVE: Clear corneal cataract incisions without sutures allow for rapid visual rehabilitation after phacoemulsification but might be associated with an increased risk of postoperative infection. The goal of this study was to examine in vitro dynamic changes in unhealed clear corneal cataract incisions that might adversely affect the risk of intraocular infection. DESIGN: Laboratory investigation. METHODS: Self-sealing clear corneal incisions were created in cadaveric human and rabbit eyes, and intraocular pressure was controlled with an infusion cannula. Incisions were imaged in real time using optical coherence tomography as intraocular pressure was varied. Using an artificial anterior chamber, India ink was applied to the surface of cadaveric human corneas with clear corneal incisions to detect possible flow of surface fluid along the incision. Intraocular pressure was varied by raising and lowering the infusion bottle so as to simulate the variation in intraocular pressure that would occur with successive blinks. RESULTS: Optical coherence tomography demonstrated variation of corneal wound morphology in response to changes in intraocular pressure. Higher intraocular pressures were associated with close apposition of the wound edges, with no tendency for wound leakage. At low intraocular pressures, however, wound edges tended to gape, starting at the internal aspect of the wound. One incision opened along the entire length, allowing fluid flow across the cornea. Histologic examination revealed India ink particles in all incisions for up to three fourths of the length of the wound. CONCLUSIONS: Transient reduction of intraocular pressure might result in poor wound apposition in clear corneal incisions, with the potential for fluid flow across the cornea and into the anterior chamber, with the attendant risk of endophthalmitis.

Animals↗

Enhancing alkylating agent resistance through ERCC2 gene transfection in human glioma cell line.

OBJECTIVE: To confirm the enhancing effect of excision repair cross complementing rodent repair deficiency gene 2 (ERCC2) on alkylating agents resistance. METHODS: The authors constructed a pcDNA3-ERCC2 plasmid. The pcDNA3-ERCC2 was transfected into a selected ERCC2 negative human glioma cell line, SKMG-4, using liposome-mediated transfection. After G418 selection, a stable transfected cell line was obtained and tested for cytotoxicity of several alkylating agents. RESULTS: The stable transfectant was obtained and confirmed by RT-PCR as well as Western blot analysis to be strongly expressing ERCC2 at both mRNA and protein levels. The IC(90) ( micro mol/L) of two alkylating agents, cisplatin and melphalan, increased from 1.0 to 1.75 (75%) and 5.6 to 9.0 (61%), respectively, compared with control cell line. CONCLUSION: The present data provided evidences and confirmed the authors' previous results that ERCC2 contributes, at least partially, to alkylating agent resistance in human glioma cell line.

Antineoplastic Agents, Alkylating↗

Clinical testing of a photoacoustic probe for port wine stain depth determination.

BACKGROUND AND OBJECTIVE: Successful laser treatment of port wine stain (PWS) birthmarks requires knowledge of lesion geometry. Laser parameters, such as pulse duration, wavelength, and radiant exposure, and other treatment parameters, such as cryogen spurt duration, need to be optimized according to epidermal melanin content and lesion depth. We designed, constructed, and clinically tested a photoacoustic probe for PWS depth determination. STUDY DESIGN/MATERIALS AND METHODS: Energy from a frequency-doubled, Nd:YAG laser (lambda=532 nm, tau(p)=4 nanoseconds) was coupled into two 1,500 mum optical fibers fitted into an acrylic handpiece containing a piezoelectric acoustic detector. Laser light induced photoacoustic waves in tissue phantoms and a patient's PWS. The photoacoustic propagation time was used to calculate the depth of the embedded absorbers and PWS lesion. RESULTS: Calculated chromophore depths in tissue phantoms were within 10% of the actual depths of the phantoms. PWS depths were calculated as the sum of the epidermal thickness, determined by optical coherence tomography (OCT), and the epidermal-to-PWS thickness, determined photoacoustically. PWS depths were all in the range of 310-570 microm. The experimentally determined PWS depths were within 20% of those measured by optical Doppler tomography (ODT). CONCLUSIONS: PWS lesion depth can be determined by a photoacoustic method that utilizes acoustic propagation time.

Dermatology↗