Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging.
The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.
Cornell University, The Methodist Hospital Research Institute, Weill Cornell Medical College, Department of Systems Medicine and Bioengineering, Houston, Texas 77030, USA.
Liang
L
Gao
Ahmad A
AA
Hammoudi
Fuhai
F
Li
Michael J
MJ
Thrall
Philip T
PT
Cagle
Yuanxin
Y
Chen
Jian
J
Yang
Xiaofeng
X
Xia
Yubo
Y
Fan
Yehia
Y
Massoud
Zhiyong
Z
Wang
Stephen T C
ST
Wong
D000465:Algorithms; D000818:Animals; D002138:Calibration; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D003937:Diagnosis, Differential; D004338:Drug Combinations; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007797:Laminin / Q000737:chemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008495:Medical Oncology / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055095:Optics and Photonics / Q000379:methods; D010363:Pattern Recognition, Automated; D011509:Proteoglycans / Q000737:chemistry; D015203:Reproducibility of Results
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen