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PDF file - 161K, Figure 1: Schematic diagrams of the imaging systems used in this study. Supplementary Figure 2: Multimodal imaging at the floor-of-mouth in a 73-year old female patient.

PDF file - 30K, Table 1: Criteria used by the surgeon to classify measurement sites Supplementary Table 2: Scoring criteria for IHC stained sites Supplementary Table 3: Distribution of measurement sites by anatomical location Supplementary Table 4: Distribution of measurement sites by clinical impression and pathology diagnosis

We developed an automated frame selection algorithm for high-resolution microendoscopy video sequences. The algorithm rapidly selects a representative frame with minimal motion artifact from a short video sequence, enabling fully automated image analysis at the point-of-care. The algorithm was evaluated by quantitative comparison of diagnostically relevant image features and diagnostic classification results obtained using automated frame selection versus manual frame selection. A data set consisting of video sequences collected in vivo from 100 oral sites and 167 esophageal sites was used in the analysis. The area under the receiver operating characteristic curve was 0.78 (automated selection) versus 0.82 (manual selection) for oral sites, and 0.93 (automated selection) versus 0.92 (manual selection) for esophageal sites. The implementation of fully automated high-resolution microendoscopy at the point-of-care has the potential to reduce the number of biopsies needed for accurate diagnosis of precancer and cancer in low-resource settings where there may be limited infrastructure and personnel for standard histologic analysis.

We developed an automated frame selection algorithm for high resolution microendoscope images. The algorithm rapidly selects a representative frame with minimal motion artifact from a short video sequence, enabling fully automated image analysis at the point-of-care. The performance of the algorithm was evaluated by comparing automatically selected frames to manually selected frames using quantitative image parameters. The implementation of fully automated high-resolution microendoscopy at the point-of-care has the potential to reduce the number of biopsies needed for accurate diagnosis of precancer and cancer in low-resource settings, where there may be limited infrastructure and personnel for standard histologic analysis.

Objectives:1) Describe 2 noninvasive optical techniques, widefield autofluorescence imaging (AFI) and optical spectroscopy, that may be used in conjunction with conventional oral examination (COE) for long-term surveillance of patients with oral potentially malignant disorders (OPMD). 2) Present images and spectra collected from patients with OPMD using AFI and spectroscopy over a 33-month surveillance period, and compare results to clinical observations and patient outcomes over that time period.Methods:Patients undergoing routine follow-up surveillance for OPMD were enrolled in a longitudinal optical imaging study. The patients were monitored over time with COE, AFI, and spectroscopy. AFI was used to observe natural tissue fluorescence over a 4-5 cm field of view. Spectroscopy was used to obtain reflectance and fluorescence spectra from selected sites within the oral cavity. The images and spectra collected from these patients were evaluated for changes over time and compared to clinical observations an...

If detected early, oral cancer is eminently curable. However, survival rates for oral cancer patients remain low, largely due to late-stage diagnosis and subsequent difficulty of treatment. To improve clinicians' ability to detect early disease and to treat advanced cancers, we developed a multimodal optical imaging system (MMIS) to evaluate tissue in situ, at macroscopic and microscopic scales. The MMIS was used to measure 100 anatomic sites in 30 patients, correctly classifying 98% of pathologically confirmed normal tissue sites, and 95% of sites graded as moderate dysplasia, severe dysplasia, or cancer. When used alone, MMIS classification accuracy was 35% for sites determined by pathology as mild dysplasia. However, MMIS measurements correlated with expression of candidate molecular markers in 87% of sites with mild dysplasia. These findings support the ability of noninvasive multimodal optical imaging to accurately identify neoplastic tissue and premalignant lesions. This in turn may have considerable impact on detection and treatment of patients with oral cancer and other epithelial malignancies. Cancer Prev Res; 5(6); 801–9. ©2012 AACR.

Dysplastic and cancerous alterations in oral tissue can be detected noninvasively in vivo using optical techniques including autofluorescence imaging, high-resolution imaging, and spectroscopy. Interim results are presented from a longitudinal study in which optical imaging and spectroscopy were used to evaluate the progression of lesions over time in patients at high risk for development of oral cancer. Over 100 patients with oral potentially malignant disorders have been enrolled in the study to date. Areas of concern in the oral cavity are measured using widefield autofluorescence imaging and depth-sensitive optical spectroscopy during successive clinical visits. Autofluorescence intensity patterns and autofluorescence spectra are tracked over time and correlated with clinical observations. Patients whose lesions progress and who undergo surgery are also measured in the operating room immediately prior to surgery using autofluorescence imaging and spectroscopy, with the addition of intraoperative high-resolution imaging to characterize nuclear size, nuclear crowding, and tissue architecture at selected sites. Optical measurements are compared to histopathology results from biopsies and surgical specimens collected from the measured sites. Autofluorescence imaging and spectroscopy measurements are continued during post-surgery followup visits. We examined correlations between clinical impression and optical classification over time with an average followup period of 4 months. The data collected to date suggest that multimodal optical techniques may aid in noninvasive monitoring of the progression of oral premalignant lesions, biopsy site selection, and accurate delineation of lesion extent during surgery.

Introduction: Patients with oral leukoplakia and other oral potentially malignant disorders (OPMD) have an increased risk for oral cancer development. Extensive research efforts are currently directed toward identification of agents which can prevent or delay progression to invasive carcinoma in these high risk patients. Although cancer development is the ideal endpoint to monitor for efficacy, years may elapse before malignant progression. Many clinical trials therefore utilize surrogate endpoints such as clinical appearance or pathologic grade of dysplasia to assess response to study agents. The subjective nature of clinical examination and potential for sampling error with small biopsy samples may limit the ability of oral chemoprevention trials to accurately evaluate the potential efficacy of study agents in patients with OPMD based on clinical examination and/or pathologic evaluation of biopsy samples. The purpose of this study is to evaluate the feasibility of using noninvasive optical imaging approaches for quantitative comparisons of oral lesions in patients participating in an oral cancer chemoprevention trial. Material and Methods: Twenty-three patients with visible oral lesions enrolled on the Erlotinib Prevention of Oral Cancer chemoprevention trial (EPOC) were simultaneously enrolled in diagnostic optical imaging and spectroscopy trials. EPOC is a multicenter trial to test the ability of an epidermal growth factor receptor (EGFR) inhibitor to reduce the incidence of oral cancer in high-risk patients. These 23 patients are also being followed over time with standard clinical examination, autofluorescence imaging (AFI), and optical spectroscopy. The AFI device captures autofluorescence images of a 4-5 cm diameter region of oral mucosa using an excitation wavelength of 405 nm, optical filters, and a camera. The spectroscopy device collects autofluorescence and reflectance spectra from selected sites using a 4 mm diameter fiber optic probe. Normalized red:green fluorescence intensity ratios from AFI and posterior probability risk scores generated by an algorithm from spectroscopy exams are recorded. Objective optical data from successive exams over time are compared to clinical exam and pathologic results from any corresponding biopsies. Results: During the 30-month period from February 2010 to August 2012 a total of 89 in vivo measurement sessions were carried out, producing data from 64 unique oral sites in 23 subjects. Of the 64 sites tracked, there were 45 corresponding histopathologic diagnoses available at some point during the study period. To date, 18 of the patients have been measured over the course of three or more visits. Conclusion: Results illustrate a potential for objective optical diagnostic evaluations to assist in monitoring response to test agents during oral chemoprevention trials. Citation Format: Jana M. Howe, Sharon Mondrik, Richard Schwarz, Tim Quang, Vijayashree Bhattar, Sohini Dhar, Mary K. Quinn, William William, Jr., Michelle D. Williams, Rebecca Richards-Kortum, Ann M. Gillenwater. Assessment of quantitative optical measurements of mucosal lesions as a surrogate biomarker in patients participating in an oral cancer chemoprevention trial. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B109.

Interim results are presented from a longitudinal study in which optical imaging and spectroscopy are used to monitor progression of oral premalignant lesions. A total of 447 sites in 120 patients were tracked over time.