Lung cancer is the leading cause of cancer related death accounting for more deaths than breast, prostate and colon combined. Early diagnosis is critical to patient survival, however the vast majority of lung malignancies are detected only once symptoms arise and the cancer has spread, at which time patients have little chance of cure. Macroscopic imaging modalities including CT and bronchoscopy have made significant strides in increasing early detection; however they do not have the required specificity to diagnose malignancy. Diagnosis must be made on the microscopic level, which at present can only be accomplished with excisional biopsy. Unfortunately, low-risk bronchoscopic techniques for retrieving biopsy samples are hampered by low diagnostic yields, and trans-thoracic and surgical approaches carry higher intrinsic risk of complications. Given the very high false positive rates of these macroscopic imaging platforms it is imperative that high-risk procedures are avoided and the diagnostic accuracy of lower-risk approaches is greatly improved. In this proposal we aim to dramatically increase the diagnostic yield of low-risk bronchial biopsy using novel optical imaging tools to locally guide biopsy site selection ensuring that diagnostic quality samples are obtained for both histopathology and molecular profiling. Specifically, we will develop and translate polarization-sensitive optical frequency domain imaging (PS-OFDI) systems, and novel catheters for conducting PS-OFDI of the airways and peripheral lung. We will develop and validate diagnostic criteria for evaluating the PS-OFDI images of lung cancer pathology, and we will conduct clinical studies to demonstrate the improvement in biopsy yield over conventional approaches. This work will leverage the expertise, resources and ongoing collaborative ties between investigators at Massachusetts General Hospital and NinePoint Medical. Together the strategic alliance already formed will ensure the successful translation and delivery of a powerful and robust new optical bronchoscopy tool that will likely result in an increase in the diagnostic yield of bronchial biopsy for the assessment of lung cancer.

Public Health Relevance

The development of new optical imaging tools to conduct microscopy in patients to guide biopsy acquisition may increase the diagnostic yield of low-risk bronchial biopsy in the assessment of lung cancer by ensuring that sufficient tumor tissue is obtained for diagnosis and molecular profiling. This may lead to fewer unnecessary high-risk surgical procedures for diagnosis, or delays in diagnosis due to serial CT imaging and, when combined with appropriate screening techniques, may lead to earlier detection and subsequent treatment of lung cancer, which will ultimately save lives.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA167827-03
Application #
8837455
Study Section
Special Emphasis Panel (ZRG1-SBIB-X (57))
Program Officer
Baker, Houston
Project Start
2013-04-19
Project End
2018-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
3
Fiscal Year
2015
Total Cost
$533,603
Indirect Cost
$168,695
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Shostak, Eugene; Hariri, Lida P; Cheng, George Z et al. (2018) Needle-based Optical Coherence Tomography to Guide Transbronchial Lymph Node Biopsy. J Bronchology Interv Pulmonol 25:189-197
Hariri, Lida P; Adams, David C; Wain, John C et al. (2018) Endobronchial Optical Coherence Tomography for Low-Risk Microscopic Assessment and Diagnosis of Idiopathic Pulmonary Fibrosis In Vivo. Am J Respir Crit Care Med 197:949-952
Hariri, Lida P; Adams, David C; Wain, John C et al. (2018) Reply to Wijmans et al.: Optical Coherence Tomography: A Valuable Novel Tool for Assessing the Alveolar Compartment in Interstitial Lung Disease? Am J Respir Crit Care Med 197:1232-1233
Adams, David C; Hariri, Lida P; Miller, Alyssa J et al. (2016) Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo. Sci Transl Med 8:359ra131
Cho, Josalyn L; Ling, Morris F; Adams, David C et al. (2016) Allergic asthma is distinguished by sensitivity of allergen-specific CD4+ T cells and airway structural cells to type 2 inflammation. Sci Transl Med 8:359ra132
Hariri, Lida P; Mino-Kenudson, Mari; Lanuti, Michael et al. (2015) Diagnosing lung carcinomas with optical coherence tomography. Ann Am Thorac Soc 12:193-201
Hariri, Lida P; Mino-Kenudson, Mari; Applegate, Matthew B et al. (2013) Toward the guidance of transbronchial biopsy: identifying pulmonary nodules with optical coherence tomography. Chest 144:1261-1268