Wednesday, April 1, 2015

Detecting micro changes in cancer cells with a new microscope

Korea: A Korean research team has developed a high-resolution optical microscope that can monitor micro changes in organs or skin cells of the human body. As the newly developed optical microscope can detect changes in the epidermal nucleus, where cancer cells mainly develop, it is expected to substantially improve early detection of diseases, including cancer.

Eighty percent of cancer cells are discovered within a depth of 1 to 3 mm in the epidermis of the body’s skin or the surface of organs. Early stage cancer cells multiply by cell division, evolving into a mass (tumor). CT, MRI or sonography, which are used to detect early stage cancer cells, can view the entire inside of the body, but due to their low-resolution, they can only detect cancer cells once they have grown into a large tumor. In contrast, an optical telescope that uses light is relatively less harmful to the body than CT, MRI, or sonography, as well as affordable, while providing high-resolution imaging to show microcells.

Therefore, the technology is used to detect diseases in their early stage via colonoscopy or gastroscopy. However, its imaging depth has remained extremely shallow because of multiple elastic light scattering, which irregularly changes the propagation direction of light waves carrying information about the object. Due to this scattering, the observable depth with high resolution is limited to just dozens of microns (㎛, 10-6m), which means that achieving images of deeper cells requires cutting biological tissue.

When a ray of light is reflected to thick scattering media, it undergoes multiple scattering. Biological tissues are the representative scattering media, and the light waves are reflected by the complex structures of the cell, such as the nucleuses, protoplasm, and walls.  
A Korean research team developed a new method to find single-scattered waves that carry information about the object intact. By doing so, they succeeded in gaining image information of cells over 1mm (10-3m) deep from the surface with a resolution of 1㎛ (10-6m). The depth is a world-record in the high-resolution imaging field, which helps track the growth of a cell nucleus (5㎛ thick on average). Therefore, the development is expected to allow much earlier detection of diseases, including cancer.

Professor Wonshik Choi said, “The research presents a way to significantly improve deep-tissue imaging, the unresolved issue, one of the two core elements of optical microscopy. The other factor is high resolution. Therefore, I expect that this discovery will be widely applied to various areas, including early detection of diseases or scoping of diseased tissues during surgery.”

2. Scattering media
3. Single-scattered waves ○ The waves are reflected to imaging targets without undergoing multiple scattering, which means they can deliver intact imaging information of the target area. The exponential attenuation of signal intensity within scattering media is determined by the complexity of the media. In the case of biological tissues, the intensity decreases one tenth per 100 μ. In other words, according to the exponential function formula, the single-scattered waves are reduced to one ten-billionth when the target depth is 1 mm.

4. Temporal resolution measurement ○ When light is reflected to media, the time of flight from the surface is determined by the moving path of the light within the media. When ultra-high-speed laser pulses or a ray of laser light with a wide wavelength band forms an interferometer, only the waves that reach the camera within a set time can be measured. This method also enables the measurement of the light intensity when it reaches the camera. The temporal resolution measurement is widely used in optical tomographic imaging devices.

5. Interference microscope ○ As an electromagnetic wave, light is defined by phase and amplitude. The images acquired by a general optical microscope signify the light intensity from the imaging target, which is determined by amplitude. Meanwhile, the phase delivers information about the propagation direction of light waves. When using a laser to form an interferometer, or a so-called interference microscope, it provides information on phase and amplitude of light waves reflected from the imaging target. The phase information also presents how light waves are curved.