The early detection of cancer is paramount when considering patient survival. Cervical cancer used to be one of the leading causes of cancer-related death in women prior to the introduction of the Papanicolaou test (Pap test) in the United States. Mortality and incidence have decreased by over 70% as a direct result of the Pap test and early screening programs. However, cervical cancer is still the second most common and third most deadly cancer for women living in low and middle-income countries (LMICs). This contrast in incidence and mortality demonstrates the need for improved low-cost screening techniques appropriate for use at the point- of-care. Recently, our laboratory, headed by my sponsor Dr. Rebecca Richards-Kortum, developed high resolution microendoscope (HRME). The HRME is capable of imaging epithelial tissue in vivo at sub-cellular resolutions for morphological changes associated with neoplasia in the cervix. However, fiber-optic microendoscopy image contrast is limited by out-of-focus light generated by scattering within tissue and can prevent analysis of nuclear morphology. While the HRME is a promising technology for point-of-care imaging, poor contrast in highly scattering tissue must be addressed. Here for my F99 dissertation research, I propose to develop and validate an HRME system capable of performing structured illumination to improve contrast and remove unwanted out-of-focus light to enable imaging of nuclear morphology in highly scattering tissue in vivo. Then, I will develop image processing algorithms to analyze images for morphological features associated with dysplasia. Finally, the system will be validated in an in vivo clinical pilot study of patients undergoing cold knife cone for diagnosed cervical adenocarcinoma in situ. My dissertation research during the F99 phase will provide training and expertise in biomedical optics and translational medicine focused on analyzing tissue morphology in vivo. During the postdoctoral K00 phase, I will focus on research pertaining to the development of molecular contrast agents used to target disease- specific markers associated with cancerous growth. The goal is to integrate these skills to build a strong foundation for a career in optical molecular imaging. The proposed training plan to achieve these goals will be under the guidance of my sponsor, Dr. Richards-Kortum at Rice University. The combined training of the F99 and K00 phases will provide the necessary skills for an independent research career in optical molecular imaging for improving the early diagnosis of cancer.
More than 530,000 new cases of cervical cancer are detected annually, resulting in 260,000 deaths, over 80% of which occur in low-resource settings. Improved early detection and treatment of precancerous and early stage cervical cancer is paramount when considering patient survival. This F99/K00 award proposal focuses on improving the early detection of cervical cancer and a training plan for building a career in improving cancer diagnosis.
| Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen et al. (2016) Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents. Proc Natl Acad Sci U S A 113:10769-73 |
