LuCED Diagnostic Tests

Specimen Prep

Sputum is the specimen used for the LuCED™ (Lung Cell Evaluation Device) test. Characterizations show that sputum from cancer patients have abnormal cells that exfoliate into the mucous stream that are brought into the sputum specimen upon collection. The specimen is fixed and stained with hematoxylin, a standard stain used by cytologists that reveals relevant aspects of cellular morphology to enable distinction of normal from abnormal cells. The specimen is further processed to remove cellular components from the specimen that are of no diagnostic value.

Cell Classification

The Cell-CT™ system produces 3D cell images which are then further processed to identify sub-cellular components of the cell and then to automatically make measurements on the cells. These measurements characterize cell features such as the volume, shape, distribution of chromatin throughout the cell, and others. The features that best describe the cell type, whether normal or abnormal, are combined together to yield a score. Because the Cell-CT represents cells comprehensively in 3D, without the ambiguity typically associated with 2D analysis, extremely accurate classification is produced.

Sensitivity and Specificity of LuCED

Two factors combine together to produce the final LuCED classification. These include: The accuracy of the cell classifier and prevalence of abnormal cells in sputum. Moreover, cancer is a slow growing disease and thus sensitivity meaningfully accrues with time. For the cancer population at large, we estimate that LuCED achieves sensitivity in excess of 95% after the second test. But high sensitivity is of little use without high specificity. Specificity determines the rate of false positive indications that may be expected. Specificity that approaches 100% for LuCED is ensured through the action of the cell classifier that eliminates almost all normal cells from review. However, the small number of cells indicated for review are then sent for visual inspection using data from the Cell-CT and VisionGate developed software that simulates a conventional microscope.

Specimen Analysis Times

The speed of the Cell-CT™ and the number of cells needed for analysis determine the time required to analyze a sputum specimen. We currently estimate that specimen analysis times will be in the 20 minute range.

Triage using LuCED

The cell classifier score is set up to yield low values for normal cells, values in the mid-range for dysplastic cells, and high values for cancer cells. Thus, the maximum classifier score for all cells analyzed expresses the highest degree of abnormality for the case. Triage may be fostered by applying a series of thresholds to this maximum value. We currently envision four triage points based for LuCED:

1. Low cell classifier values – patient is asked to return for screening at the normal frequency.
2. Classifier values consistent with Moderate Dysplasia – patent is asked to return for screening at an increased rate.
3. Classifier values consistent with Marked Dysplasia – patient is triaged for work-up by helical X-ray CT.
4. Classifier values consistent with Cancer – patient is triaged for work-up by diagnostic X-ray CT and possibly other localizing techniques such as bronchoscopy.

Cost Effectiveness of LuCED

Costs associated with the LuCED test have been assessed in the recent e-poster, presented at the 2009 meeting of the IASLC. This work shows that LuCED costs and efficacy are within the ranges for other cancer screening programs such as mammography.