Novel bio-imaging system, opening a new horizon for disease therapy studies

“The small intestine is a major organ in which the digestion of ingested foods and absorption of nutrients occur. Since the small intestine moves constantly inside the body, it was difficult to take cellular-level high resolution images of the same points for a prolonged period of time. Against this backdrop, this study attempted high-resolution imaging of the interior of the intestinal villi moving at a fast speed, using a video-rate confocal scanning laser microscope capable of taking 30 images per second. A new custom-built imaging chamber was used in this study, which could help to minimize the intestinal movement and maintain the temperature and humidity of the extracorporeal small intestine of the lab mice used. This imaging chamber allowed real-time monitoring of the absorption process of various substances in the intestine. The result of this study is expected to contribute to finding new medication delivery mechanisms where the lipid-soluble drugs are absorbed via intestinal lacteals, while the level of hepatotoxicity can be minimized.”

High-resolution imaging technology, accelerating advancement in biomedical science

The absorption process occurring in the small intestine is a matter of great interest in the field of oral medication development. Unlike water-soluble medication metabolized in the liver, which has relatively poor efficacy, lipid-soluble drugs can be more effective as they can directly enter systemic circulation when the ingested drug ingredients are absorbed through lacteals along with lipid-soluble nutrients, circumventing the first-pass metabolism in the liver.

In order to achieve optimized medication delivery through the lacteals, it is important to understand the absorption process of the lipid-soluble nutrients such as fatty acids and glycerol. The conventional method in which the samples are taken at specific times, however, has a number of limitations: the cellular-level analysis of the consecutive absorption processes by time was challenging, not to mention the difficulty of taking intestinal images of the same spots for a long time at cellular-level high resolution. For these reasons, a study on real-time high-resolution imaging technology for intestinal lipid absorption conducted by Professor Kim, Pilhan and his team at KIHST, is in the limelight as revolutionary research in the field of biomedical science.

Professor Kim first got interested in biomedical science when he was a researcher at the Harvard Medical School as a Ph.D. in electronic engineering. In 2011, Professor Koh, Gou Young at Graduate School of Medical Science & Engineering (GSMSE), KAIST, suggested a study on lipid absorption at the intestinal villi to Professor Kim. Since Prof. Kim successfully had built a high-speed laser-scanning confocal microscope through his research at that time, they decided to conduct the research jointly, combining basic biology and medical science. When they first started the study, Prof. Koh had transgenic mice that express green fluorescent protein (GFP) in the lacteal of villi. In addition to that, a customized imaging chamber that could help the intestinal imaging process of the mice was built during the course of their joint study. Through this chamber, images were taken of the process in which the red fluorescence-tagged fatty acids were absorbed through the green-fluorescent lacteal in the villi of the mice.

There was a challenge during the study as well: the fatty acids were not constantly absorbed into the intestinal villi when a cover glass was put on the inner wall of the small intestine in the imaging chamber. This problem was solved by exchanging the cover glass with a detachable one. After this fix, images were successfully taken of the process of the fatty acids being smoothly absorbed.

During the course of this research, Prof. Kim and his team found the cyclical contractility and relaxation of the lacteals for the first time ever, which was quite an unexpected breakthrough. By using a video-rate confocal scanning laser microscope, the influences of the cyclical contraction of the small intestine, which was not captured by the conventional microscope due to constant intestinal movement, on the absorption of the fatty acids was identified. Following these findings, the exact mechanism of how these movements are adjusted was also unveiled.

This study was published in the online edition of The Journal of Clinical Investigation (JCI), (Impact Factor 13.261), one of the most prominent academic journals in the biomedical science field, in Oct 5, 2015. It was also introduced in the Nov, 2015 issue of the JCI This Month as a noteworthy article under the ‘Editor’s Pick’ section. It is expected that the result of this study may accelerate the development of new drugs having higher intestinal absorption rates than conventional oral medication. This study will also greatly contribute to the advancement of the study on small intestinal diseases going forward.

Prof. Kim, Pilhan
2015 Annual Report