Brian J. F. Wong

Optical coherence tomography of the rat cochlea

Optical coherence tomography (OCT) was used to image the internal structure of a rat cochlea (ex vivo). Immediately following sacrifice, the temporal bone of a Sprague-Dawley rat was harvested. Axial OCT cross sectional images (over regions of interest, 1x1 mm-2x8 mm) were obtained with a spatial resolution of 10-15 microm. The osseous borders of the lateral membranous labyrinth overlying the cochlea and the scala vestibuli, media, and tympani, which were well demarcated by the modiolus, Reissners and the basilar membranes, were clearly identified. OCT can be used to image internal structures in the cochlea without violating the osseous labyrinth using simple surgical exposure of the promontory, and may potentially be used to diagnose inner ear pathology in vivo in both animal and human subjects labyrinth.

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 μm. 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.

Imaging the Internal Structure of the Rat Cochlea Using Optical Coherence Tomography at 0.827 μm and 1.3 μm

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 μm and 827 nm, respectively. Images (1.87 × 2.00 mm or 1.87 × 1.00 mm, 10 × 10 μm pixel resolution) were acquired at a frame rate of 1 Hz. Cross-sectional images at 100-μm 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. (Otolaryngol Head Neck Surg 2004;130:334–38.)

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.

An analysis of the Candida albicans genome database for soluble secreted proteins using computer-based prediction algorithms.

We sought to identify all genes in the Candida albicans genome database whose deduced proteins would likely be soluble secreted proteins (the secretome). While certain C. albicans secretory proteins have been studied in detail, more data on the entire secretome is needed. One approach to rapidly predict the functions of an entire proteome is to utilize genomic database information and prediction algorithms. Thus, we used a set of prediction algorithms to computationally define a potential C. albicans secretome. We first assembled a validation set of 47 C. albicans proteins that are known to be secreted and 47 that are known not to be secreted. The presence or absence of an N‐terminal signal peptide was correctly predicted by SignalP version 2.0 in 47 of 47 known secreted proteins and in 47 of 47 known non‐secreted proteins. When all 6165 C. albicans ORFs from CandidaDB were analysed with SignalP, 495 ORFs were predicted to encode proteins with N‐terminal signal peptides. In the set of 495 deduced proteins with N‐terminal signal peptides, 350 were predicted to have no transmembrane domains (or a single transmembrane domain at the extreme N‐terminus) and 300 of these were predicted not to be GPI‐anchored. TargetP was used to eliminate proteins with mitochondrial targeting signals, and the final computationally‐predicted C. albicans secretome was estimated to consist of up to 283 ORFs. The C. albicans secretome database is available at http://info.med.yale.edu/intmed/infdis/candida/ Copyright

Lemierre syndrome: a pediatric case series and review of literature.

BACKGROUND Lemierre syndrome is a rare disease of the head and neck often affecting adolescents and young adults. Classically, infection begins in the oropharynx with thrombosis of the tonsillar veins followed by involvement of the parapharyngeal space and the internal jugular vein. Septicemia and pulmonary lesions develop as infection spreads via septic emboli. Although a rare entity in modern times, Lemierre syndrome remains a disease of considerable morbidity and potential mortality. METHODS This was a retrospective review of 3 cases and associated literature. RESULTS A common 1- to 2-week history of fever, sore throat, neck pain, and fatigue was observed in all patients. Patient 1 developed right facial swelling, neck tenderness, trismus, and tonsillar exudate. Patient 2 displayed right tonsillar erythema and enlargement with right neck tenderness. Patient 3 revealed bilateral tonsillar enlargement with exudate and left neck tenderness. Subsequent studies included blood cultures and computed tomography, after which empiric antibiotic therapy was started. Patient 1 underwent drainage of a right peritonsillar abscess, right pressure equalization tube placement, and ligation of the right external jugular vein. He subsequently developed subdural empyemas, cavernous sinus thrombosis, and carotid artery narrowing and required 9 weeks of antibiotic therapy. Patients 2 and 3 developed pulmonary lesions and received 6 weeks of antibiotic therapy. Timing was crucial in all cases. CONCLUSIONS Lemierre syndrome is a rare but severe opportunistic infection with poor prognostic outcomes if left untreated. Early diagnosis and treatment is essential. Aggressive antibiotic therapy coupled with surgical intervention, when necessary, provides excellent outcomes.

In vivo three-dimensional spectral domain endoscopic optical coherence tomography using a microelectromechanical system mirror

A biopsy is a well-known medical test used to evaluate tissue abnormality. Biopsy specimens are invasively taken from part of a lesion and visualized by microscope after chemical treatment. However, diagnosis by means of biopsy is not only variable due to depth and location of specimen but may also damage the specimen. In addition, only a limited number of specimens can be obtained, thus, the entire tissue morphology cannot be observed. We introduce a three-dimensional (3-D) endoscopic optical biopsy via optical coherence tomography employing a dual-axis microelectromechanical system scanning mirror. Since this technique provides high-resolution, noninvasive, direct, and multiple visualization of tissue, it could function as a clinical biopsy with advanced performance. The device was integrated with a conventional endoscope and utilized to generate in vivo 3-D clinical images in humans and animals.

Stress Relaxation of Porcine Septal Cartilage During Nd:YAG (λ=1.32 μm) Laser Irradiation: Mechanical, Optical, and Thermal Responses.

Laser-assisted cartilage reshaping is mediated by thermally induced stress relaxation, and may be used to alter cartilage morphology for reconstructive surgical procedures in the upper airway and face without carving, morselizing, or suturing. Internal stress σ(t), integrated backscattered light intensity I(t) from a He-Ne probe laser (λ=632.8 nm), and radiometric surface temperature Sc(t) were measured during the reshaping of porcine nasal septal cartilage using a pulsed Nd:YAG laser (λ=1.32 μm). Internal stress and integrated backscattered light intensity were observed to increase, plateau, and then decrease in similar ways during laser irradiation. The plateau region occurred when the cartilage front surface temperature approached 65 °C. I(t) was utilized in a feedback control procedure to reshape cartilage specimens from a flat to a curved geometry. Immediately following laser irradiation, the tissues were rehydrated in normal saline for 15 min while wrapped around a small dowel. A stable shape change was retained for 21 days while the specimens were stored in normal saline at 5 °C. The backscattered light intensity signal mirrors underlying changes in internal stress, and further rate of change or slope of I(t) is nearly zero when the surface temperature reaches about 65 °C. Measurements of I(t) (or, equivalently, the fractional change in integrated backscattered light intensity ΔI(t)/I0) may be used to control the process of laser-assisted cartilage reshaping and minimize nonspecific thermal injury due to uncontrolled heating.

A Role for Fibroblasts in Mediating the Effects of Tobacco-Induced Epithelial Cell Growth and Invasion

Cigarette smoke and smokeless tobacco extracts contain multiple carcinogenic compounds, but little is known about the mechanisms by which tumors develop and progress upon chronic exposure to carcinogens such as those present in tobacco products. Here, we examine the effects of smokeless tobacco extracts on human oral fibroblasts. We show that smokeless tobacco extracts elevated the levels of intracellular reactive oxygen, oxidative DNA damage, and DNA double-strand breaks in a dose-dependent manner. Extended exposure to extracts induced fibroblasts to undergo a senescence-like growth arrest, with striking accompanying changes in the secretory phenotype. Using cocultures of smokeless tobacco extracts–exposed fibroblasts and immortalized but nontumorigenic keratinocytes, we further show that factors secreted by extracts-modified fibroblasts increase the proliferation and invasiveness of partially transformed epithelial cells, but not their normal counterparts. In addition, smokeless tobacco extracts–exposed fibroblasts caused partially transformed keratinocytes to lose the expression of E-cadherin and ZO-1, as well as involucrin, changes that are indicative of compromised epithelial function and commonly associated with malignant progression. Together, our results suggest that fibroblasts may contribute to tumorigenesis indirectly by increasing epithelial cell aggressiveness. Thus, tobacco may not only initiate mutagenic changes in epithelial cells but also promote the growth and invasion of mutant cells by creating a procarcinogenic stromal environment. (Mol Cancer Res 2008;6(7):1085–98)

Measurement of radiometric surface temperature and integrated backscattered light intensity during feedback-controlled laser-assisted cartilage reshaping

Cartilage undergoes characteristic mechanical stress relaxation following laser irradiation below the ablation threshold. Porcine auricular cartilage (1–2 mm thickness) was irradiated with a Nd:YAG laser (λ=1.32 μm) at two power levels (W/cm2). Surface temperature (Sc(t) (°C)) (monitored using a single element HgCdTe infrared detector, 10-14 μm spectral range), and integrated back scattered light intensityI(t) were measured during laser irradiation. A HeNe laser beam (λ=632.8 nm) was incident on the back surface of the cartilage specimen and fractional integrated backscattered light intensity was measured using an integrating sphere anda silicon photodiode. Laser irradiation (5.83 W/cm2, 50 Hz pulse repetition rate (PRR)) continued until surface temperature reached approximately 70°C, during which cartilage mechanical stress relaxation was observed. Integrated back scattered light intensity reached a plateau at about 70°C). At higher laser power (39.45 W/cm2, 50 Hz PRR), a feedback-controlled cryogen spray was used to maintain surface temperature below 50°C. A similar plateau response was noted in integrated backscattered light intensity. This signal may be used to optimise the process of stress relaxation in laser cartilage reshaping. Several clinical applications involving reconstructive surgery are proposed.