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Biomedical subjects

Zhongping Chen

Publications and source records attributed to Zhongping Chen.

At least 19 recordsLinked to original sources

Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 vis-à-vis chemotherapy drug cytotoxicity in human glioma.

ERCC1 and ERCC2 have been known to belong to the nucleotide excision repair (NER) pathway and are essential to the repair of cisplatin DNA adducts. In the present study, we have examined the potential correlation of ERCC1, ERCC2 mRNA expression and single nucleotide polymorphism (SNP) to chemotherapy drug cytotoxicity from 49 human gliomas. Fresh human glioma specimens were obtained during surgery. SNPs of ERCC1 and ERCC2 was determined by single strand conformation polymorphism (SSCP) and sequencing. ERCC1 and ERCC2 expression was quantified using real-time quantitative reverse transcription-PCR. Chemotherapy drug cytotoxicity was determined by the tetrazolium (MTT) assay for cisplatin (CDDP), 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), vincristine (VCR) and teniposide (VM26). The results show that there was no statistically significant association between the C8092A polymorphism of ERCC1 or codon 312 and codon 751 polymorphisms of ERCC2 and the chemotherapy drug cytotoxicity. However there was a strong correlation between ERCC1 and ERCC2 mRNA expression levels (Spearman r = 0.42; P < 0.003). Further more, tumor samples with low ERCC1 mRNA expression levels showed enhanced CDDP cytotoxicity (P = 0.0001) while ERCC2 expression was reversely correlated with BCNU cytotoxicity (P = 0.004). In sum, Our results indicated that ERCC1 mRNA expression is associated with CDDP cytotoxicity and ERCC2 mRNA levels is related with BCNU cytotoxicity, while there was no correlation between SNP of ERCC1, ERCC2 and in vitro cytotoxicity of four anticancer drugs, CDDP, BCNU, VCR and VM26.

Adolescent↗

In vivo optical coherence tomography of the human oral cavity and oropharynx.

Optical coherence tomography (OCT) is an evolving imaging modality that combines interferometry with low-coherence light to produce high-resolution tissue imaging. Cross-sectional in vivo images were obtained using an OCT device consisting of a Michelson interferometer, 1.3-microm broadband light source, and a handheld fiberoptic imaging probe. Image pixel resolution approached 10 microm. The mucosa of the oral cavity and oropharynx were examined in 41 patients during operative endoscopy. Optical coherence tomographic imaging was combined with endoscopic photography for gross and histologic image correlation. Optical coherence tomographic images of the oral cavity and oropharynx provided microanatomical information on the epithelium, basement membrane (BM), and supporting lamina propria (LP) of the mucosa. Normal microstructures identified in these tissues included an overlying keratin layer, papillae, ducts, glands, and blood vessels. Regions of pathologic features studied included mature scar, granulation tissue, mucous cysts, leukoplakia, and invasive cancer. Optical coherence tomographic imaging showed distinct zones of normal, altered, and ablated tissue microstructures for each pathologic process studied. Abnormal findings were directly compared with regions of normal tissue or conventional histopathologic features when tissue for analysis was available. This study provides a composite series of in vivo OCT images of the oral cavity and oropharynx in a variety of normal regions and pathologic states as well as outline future applications of OCT technology.

Adult↗

Determination of characteristics of degenerative joint disease using optical coherence tomography and polarization sensitive optical coherence tomography.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. MATERIALS AND METHODS: Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. RESULTS: OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. CONCLUSIONS: The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.

Animals↗

Noninvasive measurement of ablation crater size and thermal injury after CO2 laser in the vocal cord with optical coherence tomography.

OBJECTIVE: To characterize tissue destruction after CO(2) laser-ablation of the vocal cords with the use of optical coherence tomography (OCT). STUDY DESIGN AND SETTING: OCT was used to image fresh porcine vocal cords after laser ablation. OCT and histology estimates of the ablation crater dimensions and the depth of thermal injury were obtained. RESULTS: The vocal cord substructures up to 2.29 mm in depth at 10 microm resolution, and the thermal disruption after laser ablation were identified by OCT. OCT and histology estimates of the lesion dimensions showed no significant differences. Crater depth is directly proportional to laser power, whereas crater width and the zone of thermal injury appear to be unrelated to laser power. CONCLUSIONS: OCT may be used to accurately characterize the native states and the laser-induced thermal injury of laryngeal mucosa, within the inherent limitation in its depth of penetration. OCT may be a useful diagnostic and monitoring tool in an otolaryngology practice.

Animals↗

Optical coherence tomography of laryngeal cancer.

OBJECTIVES: Optical coherence tomography (OCT) is a high-resolution optical imaging technique that produces cross-sectional images of living tissues using light in a manner similar to ultrasound. This prospective study evaluated the ability of OCT to identify the characteristics of laryngeal cancer and measure changes in the basement membrane, tissue microstructure, and the transition zone at the edge of tumors. MATERIALS AND METHODS: One hundred thirty-three patients underwent OCT examination during surgical endoscopy of the head and neck. Twenty-two patients with laryngeal cancer or a history of laryngeal cancer were imaged with a fiberoptic OCT system. Tumor and adjacent transition zones were imaged along with uninvolved subsites. OCT images were correlated with histopathology. RESULTS: Twenty-six OCT examinations were performed in 22 patients. Basement membrane disruption was seen in 18 subjects, all of whom had histology showing classic features of cancer. A transition zone to uninvolved epithelium at the tumor periphery was also often observed. In six studies, benign or premalignant processes were histologically confirmed. In three thin, superficial lesions, an intact basement membrane was observed. The basement membrane could not be identified in three other bulky exophytic, premalignant lesions, primarily because of increased superficial signal backscattering observed in pathologic tissues. CONCLUSIONS: OCT clearly identifies basement membrane violation from laryngeal cancer and can identify transition zones at the cancer margin. In bulky exophytic lesions, OCT signal may not penetrate deeply enough to show the basement membrane, but for many suspicious lesions that require exclusion of cancer, OCT shows potential for assisting in diagnostic assessment.

Aged↗

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↗