Multispectral 3D Imaging of Pre-Cancer with PFC-LSS Angle-Resolved Technique
Significance:
Esophageal cancer is currently the fastest increasing cancer in the United States. Furthermore, the symptoms of esophageal cancer - including difficulty swallowing, chest pain, or choking - generally do not appear until advanced stages of the disease. Esophageal cancer develops almost exclusively in patients with Barrett's esophagus, an otherwise benign complication of esophageal reflux that affects approximately 3 million Americans. Although the prognosis of patients diagnosed with esophageal cancer is poor, most esophageal cancers can be prevented if the disease is detected at an early dysplastic stage. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is visually indistinguishable and affects only small portion of the esophagus. Our group has recently developed a new imaging method for detection of esophageal dysplasia which in its first clinical tests successfully detected invisible precancerous dysplasia in esophagus missed by the available clinical techniques. In its current form this method lacks depth information, an important factor in detecting and evaluating dysplasia and early cancers. Thus, in this application, we propose to add depth sensitivity to our method, providing an entirely new dimension to high resolution 3D imaging of pre-cancer.
We believe that this new imaging method offers great promise for the early detection of dysplasia in various organs. If this method were to be used routinely it would be of considerable significance and importance to the public, as the pre-cancer will be diagnosed at a much earlier, currently invisible, stage when it is still treatable, and lives will be saved.
The goal of this project is to combine endoscopic compatible scanning light scattering spectroscopy (LSS) described in our paper Qiu et al. Nature Medicine 2010, with the phase function corrected (PFC) diffusion method to develop quantitative depth sensitive imaging method for guiding biopsy in real time in esophagus. The endoscopic scanning LSS strategy is to scan the entire esophagus to obtain LSS information about every 2 mm location of the epithelial surface. The LSS relates the collected optical data to the underlying optical parameters of the epithelial cells, which includes, for example, the size distribution of epithelial cell nuclei and nuclear density, the important histological diagnostic criteria used to identify the dysplastic sites. In turn, the PFC method described in our Vitkin et al. Nature Commun. 2011 paper fixes the diffusion theory near the point-of-entry, the longstanding unsolved problem in radiative transport. It appears that the combination of endoscopic scanning LSS and PFC can result in a very promising depth resolved multispectral 3D imaging approach which can provide entirely new dimension for the multispectral high resolution transcutaneous imaging of early cancer. This new method, which can be called the multispectral imaging scanning PFC-LSS method, is proposed in this application. We will build a laboratory PFC-LSS imaging setup to test the ideas of depth resolved diagnostic imaging and, at the same time, develop a mathematical approaches capable of accurate description of both the depth resolved imaging and LSS information about epithelial tissues. After testing the laboratory setup on reproducible tissue phantoms and on freshly resected esophageal tissue we will modifying our existing endoscopic scanning LSS clinical instrument to incorporate a PFC-LSS capability for high resolution 3D imaging of epithelial sites suspicious for dysplasia. We will test the performance of the new endoscopic instrument in identifying high grade dysplasia in patients with Barrett's esophagus undergoing routine surveillance endoscopy at the Interventional Endoscopy Center at BIDMC. The accuracy of the technique will be verified using clinically accepted methods of collecting biopsies from suspected areas (immediately after optical PFC-LSS data has been collected) and obtaining and comparing pathological analysis of these biopsies. We believe that PFC-LSS imaging offers great promise for the early detection of dysplasia in esophagus, and therefore unnecessary biopsies would be avoided and focal dysplastic spots would be biopsied that otherwise would be missed.
