Pancreatic cancer (PC) remains one of the most deadly cancers, with a dismal 5-year survival rate of less than 5%. Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) cytology is often performed to obtain a pathological diagnosis of suspicious pancreatic solid and cystic lesions to guide further management of patients (i.e., preoperative surgical planning or neoadjuvant treatment). However, cytology is often stymied by the average sensitivity of 80% for pancreatic solid lesions and even more dismal sensitivity of less than 30% for diagnosing malignancy in cystic lesions. The efficacy of existing tumor markers also remains sub-optimal. The major objective of this application is to explore endogenous microscopic spectral markers as potential biomarkers to improve the diagnostic accuracy of malignancy on pancreatic solid and cystic lesions. To achieve this goal, we will address the development of a novel optical instrument - multi-mode multi- dimensional partial-wave spectroscopic microscopy (MD-PWS) that provides a comprehensive assessment of multi-dimensional elastic light-scattering signals that contain a full set of 3D wave-vectors at sub-cellular or molecular level. We hypothesize that MD-PWS derived microscopic spectral markers will detect subtle structural alterations in cytologically non-malignant-appearing cells from patients with pancreatic cancer and pancreatic cyst that carries a high malignant potential, more sensitive than conventional cytology or other clinically available biomarkers. We will explore the feasibility of MD-PWS microscopic spectral markers to improve the cytological diagnosis of malignancy in pancreatic solid lesions as well as cystic lesions. MD-PWS derived microscopic spectral markers will also provide significant insights into the structural characteristics of pancreatic cells at sub-cellular level. The results from this project will serve as a justification for a multi-center collaboration to fully evaluate this technology in a clinical setting. Our long-term goal is to develop a simple, cost-effective and highly sensitive microscopy system to improve the diagnostic accuracy and development of risk stratification strategies for pancreatic cancer. Ultimately, our proposed technology could also lead to development of better diagnostic protocols for a wide variety of cancers.

Public Health Relevance

This project is significant to the public health issue of diagnosis and early detection of pancreatic cancer. The accurate diagnosis of pancreatic solid and cystic lesions is clinically challenging. A highly sensitive microscopy system to improve the diagnostic accuracy for pancreatic malignancy and high-risk cystic lesions that have a high malignant potential could help the development of risk stratification and prevention strategies for pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA152935-02
Application #
8100190
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Thurin, Magdalena
Project Start
2010-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$159,813
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Alexandrov, Sergey A; Uttam, Shikhar; Bista, Rajan K et al. (2012) Spectral encoding of spatial frequency approach for characterization of nanoscale structures. Appl Phys Lett 101:33702
Alexandrov, Sergey A; Uttam, Shikhar; Bista, Rajan K et al. (2012) Real-time quantitative visualization of 3D structural information. Opt Express 20:9203-14
Bista, Rajan K; Wang, Pin; Bhargava, Rohit et al. (2012) Nuclear nano-morphology markers of histologically normal cells detect the ""field effect"" of breast cancer. Breast Cancer Res Treat 135:115-24
Bista, Rajan K; Uttam, Shikhar; Hartman, Douglas J et al. (2012) Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model. J Biomed Opt 17:066014
Bista, Rajan K; Brentnall, Teresa A; Bronner, Mary P et al. (2011) Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia. Inflamm Bowel Dis 17:2427-35
Alexandrov, Sergey A; Uttam, Shikhar; Bista, Rajan K et al. (2011) Spectral contrast imaging microscopy. Opt Lett 36:3323-5
Bista, Rajan K; Uttam, Shikhar; Wang, Pin et al. (2011) Quantification of nanoscale nuclear refractive index changes during the cell cycle. J Biomed Opt 16:070503
Uttam, Shikhar; Bista, Rajan K; Hartman, Douglas J et al. (2011) Correction of stain variations in nuclear refractive index of clinical histology specimens. J Biomed Opt 16:116013
Wang, Pin; Bista, Rajan K; Qiu, Wei et al. (2010) An insight into statistical refractive index properties of cell internal structure via low-coherence statistical amplitude microscopy. Opt Express 18:21950-8
Wang, Pin; Bista, Rajan K; Khalbuss, Walid E et al. (2010) Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy. J Biomed Opt 15:066028