Current projects (Funded by the National Cancer Institute)
High-Resolution Microendoscopy for the Detection of Esophageal Neoplasia
Despite advances in chemoradiation therapy, the five-year survival rate for esophageal squamous cell neoplasia (ESCN) remains a dismal 15 percent due to diagnosis at a late, incurable stage. Endoscopic screening is typically performed in high-risk populations with Lugol’s iodine staining of the mucosa and targeted biopsy of abnormal (unstained) areas. While Lugol’s significantly increases the sensitivity of white light endoscopy (>95 percent), specificity remains poor (<65 percent) as inflammation and other benign mucosal changes mimic neoplasia. While confocal microendoscopy has been shown to dramatically enhance the diagnostic accuracy and yield of Lugol’s chromoendoscopy, existing platforms are costly (>$150,000) and only available in a handful of tertiary centers worldwide.
Our group has developed a portable, battery-operated, high-resolution microendoscope (mHRME) that provides subcellular images of the esophageal epithelium, delineating the cellular and morphologic changes associated with neoplasia. In a recent, single-arm pilot trial (R21), the HRME significantly increased the sensitivity and specificity of Lugol’s screening to 100 percent and 89 percent. Based on our extensive preliminary data, we are now optimizing and validating a lower-cost (<$725), tablet-based system with a software interface that provides real-time image interpretation assistance, thus facilitating usage by less-experienced clinicians in low-resource settings. This ‘optical’ approach will likely increase the efficiency, clinical impact, and cost-effectiveness of the current standard of endoscopic screening and surveillance. To validate this, we will conduct a randomized, multicenter trial of our ‘optical biopsy’ approach comparing it to the current standard of endoscopic screening/surveillance in the United States and China. In addition, we will construct, refine and analyze a disease model of ESCN to determine the effectiveness and cost-effectiveness of incorporating HRME into endoscopic screening and surveillance in both countries. Successful results can easily be translated to global cancer screening in other organs (cervix, colon, etc.).
Global Early Cancer Detection:
Academic-Industrial Partnership to Develop and Test Esophageal Cancer Imaging Tools
Esophageal adenocarcinoma (EAC) has one of the fastest rising rates of incidence in the United States. Unfortunately, the five-year-survival for patients diagnosed with EAC is only 10 percent. EAC develops primarily in patients with Barrett's esophagus (BE). Endoscopic screening and biopsy is recommended for at-risk individuals. However, standard white-light endoscopic examination frequently misses areas of early neoplasia, which are often clinically indistinguishable from normal mucosa and/or inflammatory changes. Studies have shown that as many as 43-57 percent of early cancers can be missed by this method. Thus, there is an important need for new endoscopic technologies which improve the ability of clinicians to identify precancerous lesions and early cancers with high sensitivity and specificity.
The goal of this partnership is to develop, optimize and validate novel multi-modal, multi-scale optical imaging platforms for non-invasive, early detection of esophageal neoplasia based on optical imaging. We are collaborating with colleagues at Pentax, Inc. to design and test multi-modal endoscopic imaging systems for early detection of neoplasia in Barrett's esophagus. Widefield endoscopic imaging will be used initially to screen the surface area at risk to identify abnormal sites with high sensitivity; suspicious areas will then be imaged with much higher spatial resolution to achieve high diagnostic specificity. Both wide field and high resolution technologies will be integrated into a single endoscopic platform to increase the ease and accuracy of endoscopic cancer screening and surveillance. In sequential clinical studies, we will first separately optimize the performance of wide field endoscopic imaging and high resolution imaging. We will then integrate the wide field and high resolution imaging systems and validate their accuracy for the detection of neoplasia in subjects with Barrett's esophagus, the precursor to esophageal adenocarcinoma. Lastly, we will develop an image atlas of typical wide-field and high-resolution images, interpretation criteria, and histopathology to train future users and serve as an educational resource.
Optical Systems for In-Vivo Molecular Imaging of Cancer (with Rice University)
Cancers of the upper aero-digestive tract, which includes the oral cavity, oropharynx, and esophagus, are associated with rising incidence and uniformly poor survival, primarily due to diagnosis at a late, incurable stage. While visual screening and biopsy are recommended for at-risk individuals, the standard white-light exam frequently misses areas of early neoplasia. Moreover, incomplete resection leads to frequent recurrence. There is an important need for new imaging tools to improve early diagnosis and to guide effective treatment. Optical molecular imaging provides a unique solution to greatly improve clinical outcome. Over the last five years, we have developed optically active contrast agents, delivery formulations, and imaging systems which provide the ability to monitor and quantify molecular, functional, and morphologic biomarkers of early neoplasia.
This research project proposes to solve the clinical and technical challenges needed to realize these potential advantages in one organ system - the upper aero-digestive tract. This will be accomplished by first optimizing and translating contrast agents and imaging systems for early diagnosis of intraepithelial neoplasia. The second aim of this study will develop molecular imaging systems to enable image-guided therapy of intra-epithelial neoplasia.
The translational bioengineering studies proposed here will result in low-cost, portable tools to improve early detection and image-guided therapy of intraepithelial neoplasia in the upper aero-digestive tract, providing a foundation to extend these tools to other organ sites.