超拡大内視鏡による生体内細胞診断

Observation of a Living Cancer Cell in vivo in the Gastrointestinal Tract Using Ultra-high Magnification Endoscopy

要旨　“生体内で生きている消化管粘膜上皮を細胞レベルで観察したい”という願いから，1996年より産学共同研究による超拡大内視鏡の開発に着手した．その結果これまでに2種類の器械の開発に至った．その1つは“Endo-Microscopy”であり，レーザー共焦点顕微鏡を応用したカテーテル型プローブで“無染色”での細胞レベルの画像の獲得に成功した．これによりpitのみならず，細胞や核などの観察が可能となった．そして癌における“輝度の逆転現象”も確認された．もう1つは“Endo-Cytoscopy”であり，通常の光学レンズ系による超拡大内視鏡でcontact endoscopyの原理に基づきカテーテル型プローブを作製した（多施設共同提案）．このEndo-Cytoscopyは“染色下”に施行する．メチレンブルー染色で核のみならず核小体の観察も行え，現在のgold standardである細胞診と同様の高解像の明瞭な画像での観察が可能であった．両技術ともにそれぞれの特色を有しており，今後のさらなる展開が期待される．いずれにしても現在，生きた細胞の生体内での内視鏡観察は既に可能な時代に突入した．

　A project to observe living cancer cells in vivo was initiated around 1996, and has supplied us with two methods to observe living human cells in vivo, namely “Endo-Microscopy” and “Endo-Cytoscopy.” Both are prototypes from Olympus, Tokyo.

　“Endo-Microscopy” is based upon a technology in laser-scanning confocal microscopy. A miniaturized sensor is mounted on the distal end of a catheter probe, which collects the reflective laser beam passing through the confocal gate. Utilizing this device, a cell-component's level image is successfully obtained without dye treatment of the target tissue. In “Endo-Microscopy”, data from serial horizontal sections of the target tissue is accumulated and then analyzed, producing a computerized vertical section image of the tissue, which corresponds to the conventional histology image.

　“Endo-Cytoscopy” is another technology based on contact-type light microscopy, which has a magnifying power of more than 1,000 times. Methylene blue solution is used for vital staining. Nucleus, cell body, and nucleolus are clearly shown with high quality images which are equivalent to those of conventional cytology.

　These novel technologies potentially enable in vivo histological diagnosis and offer the new categories of “virtual biopsy” and “virtual histology.” “Virtual-” means that a living cell structure level image demands no actual tissue removal from the human body. Virtual biopsy with these devices will potentially reduce the number of biopsies during endoscopic examination. Virtual histology may also reduce the time delay in acquiring histological diagnosis.

　1) Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan