Automated 3-dimensional morphologic analysis of sputum specimens for lung cancer detection: Performance characteristics support use in lung cancer screening

David C. Wilbur, Michael G. Meyer, Chris Presley, Ralph W. Aye, Paul Zarogoulidis, Douglas W. Johnson, Nir Peled, and Alan C. Nelson. Cancer Cytopathology. 2015. doi: 10.1002/cncy.21565

LuCED testing is highly sensitive and specific for the detection of lung cancer and has potential value as an adjunctive test after suspicious LDCT findings or as a primary screening test in which LuCED-positive cases would be triaged to diagnostic CT.


The Cell-CT 3-dimensional cell imaging technology platform enables the detection of lung cancer using the noninvasive LuCED sputum test

Michael Meyer, Jon W. Hayenga, Thomas Neumann, Rahul Katdare, Chris Presley, David E. Steinhauer, Timothy M. Bell, Christy Lancaster, and Alan C. Nelson. Cancer Cytopathology. 2015. doi: 10.1002/cncy.21576

LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT, which images cells in 3 dimensions with submicron resolution. Algorithms are applied to the 3-dimensional cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist’s manual review. LuCED promotes accurate cell classification that could enable the cost-effective detection of lung cancer.


Premalignant and Malignant Cells in Sputum From Lung Cancer Patients

Thomas Neumann, Michael G. Meyer, Florence W. Patten, Fred L. Johnson, Yener S. Erozan, William J. Frable, Prabodh K. Gupta, Muhammad B. Zaman, and Alan C. Nelson. Cancer Cytopathology 117 (2009) 473-481

The objective of this study was to assess the frequency of premalignant and malignant cells in sputum from patients with lung cancer and to measure the dependence of these cells on cancer stage, histologic type, tumor size, and tumor location.

Automated cell analysis in 2D and 3D: A comparative study

Michael G. Meyer, Mark Fauver, J. Richard Rahn, Thomas Neumann, Florence W. Patten, Eric J. Seibel, and Alan C. Nelson. Pattern Recognition 42 (2009) 141-146

Optical projection tomographic microscopy is a technique that allows 3D analysis of individual cells. Theoretically, 3D morphometry would more accurately capture cellular features than 2D morphometry. To evaluate this thesis, classifiers based on 3D reconstructions of cell nuclei were compared with 2D images from the same nuclei. Human adenocarcinoma and normal lung epithelium cells were used. Testing demonstrated a three-fold reduction in the false negative rate for adenocarcinoma detection in 3D versus 2D at the same high specificity. We conclude that 3D imaging will potentially expand the horizon for automated cell analysis with broad applications in the biological sciences.


Three-dimensional imaging of single isolated cell nuclei using  optical projection tomography

Mark Fauver & Eric J. Seibel, J. Richard Rahn, Michael G. Meyer, Florence W. Patten, Thomas Neumann, and Alan C. Nelson. Optics Express 13 (2005) 4210-4223

A method is presented for imaging single isolated cell nuclei in 3D, employing computed tomographic image reconstruction. The system uses a scanning objective lens to create an extended depth-of-field (DOF) image similar to a projection or shadowgram. A microfabricated inverted v-groove allows a microcapillary tube to be rotated with sub-micron precision, and refractive index matching within 0.02 both inside and outside the tube keeps optical distortion low. Cells or bare cell nuclei are injected into the tube and imaged in 250 angular increments from 0 to 180 degrees to collect 250 extended DOF images. After these images are further aligned, the filtered backprojection algorithm is applied to compute the 3D image. To estimate the cutoff spatial frequency in the projection image, a spatial frequency ratio function is calculated by comparing the extended depth-of-field image of a typical cell nucleus to the fixed focus image. To assess loss of resolution from fixed focus image to extended DOF image to 3D reconstructed image, the 10-90% rise distance is measured for a dyed microsphere. The resolution is found to be 0.9 µm for both extended DOF images and 3D reconstructed images. Surface and translucent volume renderings and cross-sectional slices of the 3D images are shown of a stained nucleus from fibroblast and cancer cell cultures with added color histogram mapping to highlight 3D chromatin structure.

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