JP2014075999A5 - Cardiomyocyte motion detection method, cardiomyocyte culture method, drug evaluation method, image processing program, and image processing apparatus - Google Patents
Cardiomyocyte motion detection method, cardiomyocyte culture method, drug evaluation method, image processing program, and image processing apparatus Download PDFInfo
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- 210000004413 Myocytes, Cardiac Anatomy 0.000 title claims description 36
- 210000002317 cardiac myocyte Anatomy 0.000 title claims description 32
- 238000001514 detection method Methods 0.000 title claims description 16
- 239000003814 drug Substances 0.000 title claims description 10
- 229940079593 drugs Drugs 0.000 title claims description 10
- 238000011156 evaluation Methods 0.000 title claims description 7
- 210000004027 cells Anatomy 0.000 claims description 40
- 230000000877 morphologic Effects 0.000 claims description 13
- 230000000737 periodic Effects 0.000 claims description 12
- 238000003384 imaging method Methods 0.000 claims description 6
- 238000010191 image analysis Methods 0.000 claims description 4
- 230000009087 cell motility Effects 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims 3
- 230000014759 maintenance of location Effects 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 239000000284 extract Substances 0.000 description 3
- 230000002107 myocardial Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 1
Description
本発明は、幹細胞から分化した心筋細胞の運動解析するために最適な運動検出方法、心筋細胞の培養方法、薬剤評価方法、画像処理プログラム及び画像処理装置に関する。 The present invention relates to a motion detection method, a cardiomyocyte culture method, a drug evaluation method, an image processing program, and an image processing apparatus that are optimal for analyzing the motion of cardiomyocytes differentiated from stem cells.
本発明を例示する第１の態様に従えば、所定時間を隔てて、心筋細胞の候補となる細胞コロニーの時系列画像を取得することと、前記取得した前記時系列画像から前記細胞コロニーを抽出することと、前記抽出した細胞コロニーの中で動きのある動き領域を抽出することと、前記時系列画像から前記動き領域の細胞の形態的特徴量を算出することと、前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出することと、前記抽出した細胞コロニーの中で、動きの滞留領域を抽出すること、を含む心筋細胞の運動検出方法が提供される。 According to the first aspect illustrating the present invention, a time-series image of a cell colony that is a candidate for a myocardial cell is acquired at a predetermined time interval, and the cell colony is extracted from the acquired time-series image Extracting a moving region having movement in the extracted cell colony; calculating a morphological feature amount of cells in the moving region from the time-series image; and Provided is a cardiomyocyte motion detection method including detecting a periodic motion of cardiomyocytes based on a time-series change and extracting a stagnant region of motion from the extracted cell colonies. .
本発明を例示する第２の態様に従えば、コンピュータにより読み取り可能であり、撮像装置により撮影された画像を取得して画像処理する画像処理装置として前記コンピュータを機能させるための画像処理プログラムであって、前記撮像装置によって、所定時間を隔てて、心筋細胞の候補となる細胞コロニーの時系列画像を取得するステップと、前記画像処理装置によって、前記取得した前記時系列画像から前記細胞コロニーを抽出するステップと、前記画像処理装置によって、前記抽出した細胞コロニーの中で動きのある動き領域を抽出するステップと、前記画像処理装置によって、前記時系列画像から前記動き領域の細胞の形態的特徴量を算出するステップと、前記画像処理装置によって、前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出するステップと、前記画像処理装置によって、前記抽出した細胞コロニーの中で、動きの滞留領域を抽出するステップと、を前記コンピュータに実行させる画像処理プログラムが提供される。 According to a second aspect of the present invention , there is provided an image processing program that causes a computer to function as an image processing apparatus that can be read by a computer and that acquires an image captured by an imaging apparatus and performs image processing. Acquiring a time-series image of cell colonies that are candidates for cardiomyocytes with a predetermined time interval by the imaging device, and extracting the cell colony from the acquired time-series image by the image processing device. And a step of extracting a moving region in the extracted cell colony by the image processing device, and a morphological feature amount of the cell in the moving region from the time-series image by the image processing device. And calculating a heart based on a time-series change of the morphological feature amount by the image processing device. Detecting a periodic movement of the cells by the image processing apparatus, in the extracted cell colony, an image processing program executed by extracting a staying area of movement, to the computer is provided .
本発明を例示する第３の態様に従えば、撮像装置により所定時間を隔てて心筋細胞の候補となる細胞コロニーが撮影された時系列画像を取得して画像を解析する画像解析部を備えた画像処理装置であって、前記画像解析部は、前記取得した前記時系列画像から前記細胞コロニーを抽出するコロニー検出部と、前記抽出した細胞コロニーの中で動きのある動き領域を抽出する動き領域検出部と、前記時系列画像から前記動き領域の細胞の形態的特徴量を算出する特徴量算出部と、前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出する周期的運動検出部と、前記抽出した細胞コロニーの中で、動きの滞留領域を抽出する滞留領域検出部と、を備える画像処理装置が提供される。 According to the third aspect exemplifying the present invention, an image analysis unit that acquires a time-series image in which a cell colony that is a candidate for a cardiomyocyte is photographed at a predetermined time by an imaging device and analyzes the image is provided. In the image processing device, the image analysis unit includes a colony detection unit that extracts the cell colony from the acquired time-series image, and a motion region that extracts a moving region in the extracted cell colony. A detection unit; a feature amount calculation unit that calculates a morphological feature amount of the cell in the motion region from the time-series image; and a periodic motion of the myocardial cell is detected based on a time-series change of the morphological feature amount. There is provided an image processing apparatus comprising: a periodic motion detection unit that performs the above-described operation; and a stay region detection unit that extracts a stay region of movement among the extracted cell colonies .
本発明の細胞の運動検出方法、心筋細胞の培養方法、薬剤評価方法、画像処理プログラム及び画像処理装置によれば、心筋細胞の周期的な運動を正確に検出して、該細胞運動を定量的に評価・判断することが可能である。 According to the cell movement detection method, cardiomyocyte culture method, drug evaluation method, image processing program, and image processing apparatus of the present invention, the periodic movement of cardiomyocytes is accurately detected, and the cell movement is quantitatively detected. It is possible to evaluate and judge.
Claims (15)
前記取得した前記時系列画像から前記細胞コロニーを抽出することと、
前記抽出した細胞コロニーの中で動きのある動き領域を抽出することと、
前記時系列画像から前記動き領域の細胞の形態的特徴量を算出することと、
前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出することと、
前記抽出した細胞コロニーの中で、動きの滞留領域を抽出すること、
を含む心筋細胞の運動検出方法。 Obtaining a time-series image of cell colonies that are candidates for cardiomyocytes at a predetermined time interval;
And extracting said cell colonies from the time-series images, wherein the acquired,
And extracting a motion area of movement in the extracted cell colonies,
Calculating a morphological feature amount of the cell in the moving region from the time-series image;
Detecting a periodic movement of cardiomyocytes based on a time-series change of the morphological feature amount;
Extracting a movement retention region in the extracted cell colonies;
A method for detecting motion of cardiomyocytes , comprising
前記時系列画像において前記動きベクトルが検出された領域を前記動き領域として抽出する、請求項１〜３のいずれか一項に記載の心筋細胞の運動検出方法。 Detecting a motion vector between two or more images in the time-series image;
The cardiac muscle cell motion detection method according to claim 1, wherein a region where the motion vector is detected in the time-series image is extracted as the motion region.
前記時系列画像において、前記動き領域の前記動きベクトルの時系列変化と、前記形態的特徴量の時系列変化と、が同期的に検出されたときに、当該動き領域の中の周期的な運動を繰り返す細胞部位を前記拍動領域として判別する、請求項１〜５のいずれか一項に記載の心筋細胞の運動検出方法。 Detecting a motion vector between two or more images in the time-series image;
In the time-series image, when a time-series change of the motion vector of the motion region and a time-series change of the morphological feature amount are detected synchronously, a periodic motion in the motion region The method for detecting the movement of cardiomyocytes according to any one of claims 1 to 5, wherein a cell part that repeats the above is discriminated as the pulsation region.
収縮方向の前記動きベクトルから前記拍動領域の画像中の注目点を算出し、前記注目点中心の小領域から拍動中心を算出する、請求項６に記載の心筋細胞の運動検出方法。 Detecting a motion vector between two or more images in the time-series image of the pulsation region;
The cardiac muscle cell motion detection method according to claim 6 , wherein an attention point in the image of the pulsation region is calculated from the motion vector in a contraction direction, and a pulsation center is calculated from a small region at the center of the attention point.
前記運動を検出される心筋細胞の細胞コロニーの育成状態を評価することと、
前記評価の結果に基づき前記細胞コロニーの培養条件を変更すること、を含む心筋細胞の培養方法。 Detecting the movement of cardiomyocytes by the method for detecting movement of cardiomyocytes according to any one of claims 1 to 8,
Assessing the growth state of cardiomyocyte cell colonies from which the movement is detected;
A method for culturing cardiomyocytes, comprising changing the culture conditions of the cell colonies based on the result of the evaluation .
前記運動を検出される心筋細胞の細胞コロニーに所定タイミングで薬剤を滴下することと、
前記滴下される薬剤の効果を、心筋細胞の周期的な運動から評価することと、を含む薬剤評価方法。 Detecting the movement of cardiomyocytes by the method for detecting movement of cardiomyocytes according to any one of claims 1 to 8,
Dropping a drug at a predetermined timing on a cell colony of cardiomyocytes from which the movement is detected;
Evaluating the effect of the dropped drug from periodic movement of cardiomyocytes .
前記撮像装置によって、所定時間を隔てて、心筋細胞の候補となる細胞コロニーの時系列画像を取得するステップと、
前記画像処理装置によって、前記取得した前記時系列画像から前記細胞コロニーを抽出するステップと、
前記画像処理装置によって、前記抽出した細胞コロニーの中で動きのある動き領域を抽出するステップと、
前記画像処理装置によって、前記時系列画像から前記動き領域の細胞の形態的特徴量を算出するステップと、
前記画像処理装置によって、前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出するステップと、
前記画像処理装置によって、前記抽出した細胞コロニーの中で、動きの滞留領域を抽出するステップと、
を前記コンピュータに実行させる画像処理プログラム。 An image processing program that allows a computer to function as an image processing apparatus that can be read by a computer and that acquires an image captured by an imaging apparatus and performs image processing.
Obtaining a time-series image of a cell colony that is a candidate for a cardiomyocyte with a predetermined time interval by the imaging device;
By the image processing apparatus, extracting the cell colonies from the time-series images, wherein the acquired,
Extracting a motion region having motion in the extracted cell colony by the image processing device;
Calculating, by the image processing device, a morphological feature amount of a cell in the motion region from the time-series image;
Detecting, by the image processing device, periodic movement of cardiomyocytes based on a time-series change of the morphological feature amount;
In the extracted cell colony, by the image processing device, extracting a movement retention region;
An image processing program for causing the computer to execute .
前記画像解析部は、
前記取得した前記時系列画像から前記細胞コロニーを抽出するコロニー検出部と、前記抽出した細胞コロニーの中で動きのある動き領域を抽出する動き領域検出部と、前記時系列画像から前記動き領域の細胞の形態的特徴量を算出する特徴量算出部と、前記形態的特徴量の時系列変化に基づいて、心筋細胞の周期的な運動を検出する周期的運動検出部と、前記抽出した細胞コロニーの中で、動きの滞留領域を抽出する滞留領域検出部と、
を備える画像処理装置。 An image processing apparatus including an image analysis unit that acquires a time-series image in which a cell colony that is a candidate for a cardiac muscle cell is imaged at a predetermined time by an imaging device and analyzes the image,
The image analysis unit
A colony detection unit for extracting the cell colonies from the time-series images, wherein the acquired, the motion area detection unit for extracting a motion area of movement in the extracted cell colonies, from the time series images of the motion region A feature amount calculating unit for calculating a morphological feature amount of a cell , a periodic motion detecting unit for detecting a periodic motion of cardiomyocytes based on a time-series change of the morphological feature amount, and the extracted cell colony A staying area detection unit for extracting a staying area of movement,
An image processing apparatus comprising:
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