Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques.

This work reports a multimodal system for label-free tissue diagnosis combining fluorescence lifetime imaging (FLIm), ultrasound backscatter microscopy (UBM), and photoacoustic imaging (PAI). This system provides complementary biochemical, structural and functional features allowing for enhanced in vivo detection of oral carcinoma. Results from a hamster oral carcinoma model (normal, precancer and carcinoma) are presented demonstrating the ability of FLIm to delineate biochemical composition at the tissue surface, UBM and related radiofrequency parameters to identify disruptions in the tissue microarchitecture and PAI to map optical absorption associated with specific tissue morphology and physiology.

Comparison of PET imaging with 64Cu-liposomes and 18F-FDG in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch model of oral dysplasia and squamous cell carcinoma.

Purpose: Currently, 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) is the gold standard radiotracer for staging of head and neck cancer; however, the low sensitivity of this tracer can impede detection of early lesions. (64)Cu-liposomes accumulate in various cancers and provide both a sensitive tracer and an indication of the biodistribution of nanotherapeutics. Here, the accumulation of (64)Cu-liposomes in early and established cancers is assessed and compared with (18)F-FDG in a head and neck cancer model.

In vivo validation of a bimodal technique combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy for diagnosis of oral carcinoma.

Tissue diagnostic features generated by a bimodal technique integrating scanning time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model. Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and temporally resolved using a set of filters/dichroic mirrors and a fast digitizer, respectively. A 41-MHz focused transducer (37-μm axial, 65-μm lateral resolution) is used for UBM scanning.

Artificial muscle for reanimation of the paralyzed face: durability and biocompatibility in a gerbil model.

Background: Current management of permanent facial paralysis centers on nerve grafting and muscle transfer; however, limitations of those procedures call for other options.

Objectives: To determine the durability and biocompatibility of implanted artificial muscle in a gerbil model and the degree of inflammation and fibrosis at the host tissue-artificial muscle interface.

Methods: Electroactive polymer artificial muscle (EPAM) devices engineered in medical-grade silicone were implanted subcutaneously in 13 gerbils.

Comparison of effectiveness of silicone gel sheeting with microporous paper tape in the prevention of hypertrophic scarring in a rabbit model.

Objective: To determine the effectiveness of treating scars with microporous paper tape or silicone gel sheeting (SGS) in preventing hypertrophic scarring.

Methods: Forty hypertrophic scars were induced in a validated rabbit ear model. Wounds were randomized and bandaged for 30 days with either SGS (20 wounds), paper tape (20 wounds), or untreated controls (40 wounds).

Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma.

A compact clinically compatible fluorescence lifetime imaging microscopy (FLIM) system was designed and built for intraoperative disease diagnosis and validated in vivo in a hamster oral carcinogenesis model. This apparatus allows for the remote image collection via a flexible imaging probe consisting of a gradient index objective lens and a fiber bundle. Tissue autofluorescence (337 nm excitation) was imaged using an intensified CCD with a gate width down to 0.

Long-term hearing loss in gerbils with bacterial meningitis treated with superoxide dismutase.

Hypothesis: The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only prevent cochlear fibrosis and neo-ossification but also reduce hearing loss.

Background: SOD an O2-scavenger, has been shown to prevent cochlear fibrosis and neo-ossification in gerbils infected with bacterial meningitis when injected intrathecally. The objective of this study is to investigate the effects of SOD on long-term hearing loss in gerbils infected with bacterial meningitis and to assess the relationship between hearing results and the amount of fibrosis.

Gerbilline cholesteatoma development Part III. Increased proliferation index of basal keratinocytes of the tympanic membrane and external ear canal.

Objective: To quantify the rate of basal cell division for keratinizing epithelium (KE) of the tympanic membrane (TM) and external ear canal (EAC) in spontaneous and induced gerbilline cholesteatomas.

Study Design And Setting: Cholesteatomas (3 spontaneous and 5 by induction) were labeled with tritiated thymidine for autoradiography and a KE proliferation index (PI) was determined. The PI was defined as the average number of labeled cells/mm overall and per anatomic region.

Gerbilline cholesteatoma development. Part II: temporal histopathologic changes in the tympanic membrane and middle ear.

Objective: Determine the sequence of gross and histopathologic change to the normal middle ear (ME), tympanic membrane (TM), and external auditory canal (EAC) during spontaneous gerbilline cholesteatoma development.

Study Design And Setting: Sixty-six gerbils were examined weekly and periodically sacrificed for analysis.

Results: Cholesteatoma development followed this sequence: 1) slightly thickened pars flaccida (PF) without ME effusion, 2) thickened PF with ME effusion, 3) continuous buildup of EAC debris, and 4) complete occlusion of the lateral EAC.

Gerbilline cholesteatoma development Part I: Epithelial migration pattern and rate on the gerbil tympanic membrane: comparisons with human and guinea pig.

Objective: To determine the migration rate and pattern for keratin on the tympanic membrane (TM) of the gerbil and guinea pig in comparison to human data and determine which species is an appropriate model for investigating the relationship of epithelial clearance to cholesteatoma formation.

Study Design And Setting: Ink drops were placed on the TM and their locations plotted daily.

Results: Gerbils demonstrated a radial migration pattern away from the umbo, identical to that reported for humans, although the rate was 0.

Nonhuman primate models of intrauterine cytomegalovirus infection.

Congenital human cytomegalovirus (HCMV) infection has long been recognized as a threat to the developing fetus, even though studies have shown that only a subset of congenital infections results in clinical signs of disease. Among the estimated 8000 children who develop sequelae from congenital CMV infection each year in the United States alone, most suffer permanent developmental defects within the central nervous system. Because there is currently no approved vaccine for HCMV, and anti-HCMV drugs are not administered to gravid women with congenital infection because of potential toxicity to the fetus, there is a clear clinical need for effective strategies that minimize infection in the mother, transplacental transmission of the virus, and/or fetal disease.

Role of tumor necrosis factor-alpha in sensorineural hearing loss after bacterial meningitis.

Hypothesis: Blockade of tumor necrosis factor-alpha with tumor necrosis factor-alpha antibody will reduce the extent of cochlear injury and hearing loss associated with Streptococcus pneumoniae meningitis.

Background: Inflammatory mediators play a significant role in the morbidity associated with bacterial meningitis, including hearing loss and labyrinthitis ossificans. Previous studies have shown the attenuation of hearing loss by the nonspecific blockade of such pathways.

Fine structure histopathology of labyrinthitis ossificans in the gerbil model.

Labyrinthitis ossificans (LO) is the pathological deposition of new bone within the lumen of the cochlea and labyrinth. This process occurs most commonly as a result of infection or inflammation affecting the otic capsule. Trauma and vascular compromise can also lead to neo-ossification within the otic capsule.

The effects of superoxide dismutase in gerbils with bacterial meningitis.

Background: Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments.

Objective: To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis.

Increased proliferation and migration of epithelium in advancing experimental cholesteatomas.

Hypothesis: Hyperproliferative and migratory process of keratinocytes are part of the pathogenesis of cholesteatoma.

Background: Cytokeratin (CK) changes were prominent in the most rapidly expanding regions of cholesteatoma formation.

Methods: The three types of animal model-canal ligation (CL), retraction pocket (RP), and propylene glycol (PG)-were induced in Mongolian gerbils.

Expression patterns of cytokeratins in cholesteatomas: evidence of increased migration and proliferation.

Aural cholesteatoma is characterized by invading squamous epithelia with altered growth properties. Cytokeratin (CK) expression is affected in epidermal proliferative diseases and represents the alterations of keratinocyte proliferation, differentiation, and migration. In the present study, the intensity of CK immuno-expression was determined, using densitometry at various sites in experimental cholesteatoma in order to characterize changes of keratinocytes.