3D Cell Scanner Shows Promise for Breast Cancer Detection

Cell-CT™ Platform

Optical Projection Tomography

The Cell-CT uses a technique called Optical Projection Tomography to render cells in 3D. This process is illustrated for a squamous cancer cell in the video below where a cell is shown transported through the Cell-CT’s glass micro-capillary by applying pressure to a gel that embeds cells. As the capillary spins, the cell is scanned from multiple perspectives yielding a set of pseudo-projection images. These images are combined together using a method known as Filtered Back-Projection, producing the final 3D cell volume.

Color and opacity may be adjusted in the reconstruction to emphasize aspects of the cell that are of interest. This process is shown for a ciliated columnar cell.

The cell is shown in maximum intensity projection. In the center and right panels, color and opacity have been adjusted to render the cytoplasm in translucent white, the nucleus in opaque blue and the interior of the nucleus in a green to red chromatic gradient with the nucleoli rendered in opaque red. The cell is shown whole at left and center and cropped at right. Individual cillia are approximately 0.2 microns in diameter. Observation of individual cilia in the video indicates that Cell-CT resolution is at least one-half micron.

Background

Grading schemes for breast cancer diagnosis are predominantly based on pathologists’ qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.

Methodology

We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.

Principal Findings

We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p

Conclusions

Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.

Researchers at the Biodesign Institute at Arizona State University have been investigating the use of a new 3D cell imaging technology called Cell-CT to characterize subtle changes in a cell’s nuclear structure in order to improve the diagnostic accuracy and prognosis for breast cancer.

Cell-CT uses optical projection tomography to render cells in 3D and is developed by VisionGate, Inc. out of Phoenix Arizona. The Cell-CT appears to be in the process of commercialization and its operation is described on the company’s product page and demonstrated quite nicely in the video below.

VisionGate’s innovative Cell-CT technology is breaking new ground in the field of quantitative cell analysis by virtue of its unique ability to compute the true 3D internal structure of cells based on molecular optical absorption densities. The computed 3D density structure is isotropic within a cell; meaning the resolution is equal in all three spatial dimensions. Cells are not placed on slides, but rather, they are suspended in fluid and injected through a micro-capillary tube that permits multiple viewing perspectives around 360°. VisionGate’s method of 3D imaging uses state-of-the-art radiological x-ray CT tomographic image reconstruction, while utilizing visible photons rather than x-rays. The Cell-CT platform enables the quantitative analysis of the in situ 3D distribution of targeted molecular markers, stains and other absorbing structures within a cell at sub-micron resolution in a manner that links to traditional pathology, but with the third dimension.

The researchers characterized the structures of normal, benign and malignant cells using the Cell-CT platform. Their key findings were published in a recent issue of the journal PLoS ONE. Distinct structural signatures for each of the three types of cells were identified along with 42 distinct morphological and textural descriptors of cellular and nuclear structures. While a significant amount of work remains to fully validate this novel approach to breast cancer detection, it would appear to be a promising start for the Cell-CT technology.

Source : http://www.visiongate3d.com/cell-ct/cellct-platform

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