[go: up one dir, main page]

JP2004089533A - Fluorescent substance accumulating tumor boundary identification device - Google Patents

Fluorescent substance accumulating tumor boundary identification device Download PDF

Info

Publication number
JP2004089533A
JP2004089533A JP2002256991A JP2002256991A JP2004089533A JP 2004089533 A JP2004089533 A JP 2004089533A JP 2002256991 A JP2002256991 A JP 2002256991A JP 2002256991 A JP2002256991 A JP 2002256991A JP 2004089533 A JP2004089533 A JP 2004089533A
Authority
JP
Japan
Prior art keywords
fluorescent substance
light
light source
optical fiber
tumor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP2002256991A
Other languages
Japanese (ja)
Inventor
Motoji Haratou
原頭 基司
Kyojiro Nanbu
南部 恭二郎
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toshiba Corp
Original Assignee
Toshiba Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Toshiba Corp filed Critical Toshiba Corp
Priority to JP2002256991A priority Critical patent/JP2004089533A/en
Publication of JP2004089533A publication Critical patent/JP2004089533A/en
Pending legal-status Critical Current

Links

Images

Landscapes

  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Endoscopes (AREA)

Abstract

【課題】外科手術の手順を邪魔することなく、かつ、腫瘍領域を正確に識別しながら、より安全に腫瘍切除を行なえるように支援する。
【解決手段】患者PSの患部OBに集積して化学修飾を受けた蛍光物質に対し所定波長成分の励起光を照射し、且つ、その点灯及び消灯の繰り返しにより蛍光物質の励起を断続的に行なう光源部2と、この光源部2からの励起光を患部OB近傍に導き、その患部に集積した蛍光物質から放射される蛍光を入射する光ファイバ8と、この光ファイバ8を介して入射される蛍光の強度を検出する検出部3と、この検出部3により検出された光源部2の点灯及び消灯に対応する蛍光強度に基づいて蛍光物質の濃度を推定する演算装置4と、この演算装置による蛍光物質の濃度推定値を表示する表示装置5とを備える。
【選択図】 図1
An object of the present invention is to assist in performing safer tumor excision without disturbing a surgical procedure and accurately identifying a tumor region.
Kind Code: A1 An excitation light of a predetermined wavelength component is radiated to a fluorescent substance which has been accumulated on an affected part OB of a patient PS and has undergone chemical modification, and excitation of the fluorescent substance is intermittently performed by repeatedly turning on and off the fluorescent substance. A light source unit 2, an optical fiber 8 for guiding excitation light from the light source unit 2 to the vicinity of the affected area OB, and receiving fluorescence emitted from a fluorescent substance accumulated in the affected area, and entering through the optical fiber 8. A detecting unit 3 for detecting the intensity of the fluorescent light, an arithmetic unit 4 for estimating the concentration of the fluorescent substance based on the fluorescent intensity corresponding to the turning on and off of the light source unit 2 detected by the detecting unit 3; A display device 5 for displaying the estimated concentration of the fluorescent substance.
[Selection diagram] Fig. 1

Description

【0001】
【発明の属する技術分野】
本発明は、蛍光物質集積性腫瘍の境界識別装置に係り、とくに蛍光物質集積性をもつ腫瘍を外科的に切除する手術を行なうときに、その腫瘍の境界を無影灯や通常照明の点灯下でもその影響を受けずに検出しその境界表面にマーキングを施すことによりその腫瘍切除の外科手術を支援する支援装置に関する。この支援装置は、例えば、腫瘍組織と正常組織との境界が非常に重要な脳外科手術や一般の外科手術に利用可能である。
【0002】
【従来の技術】
臨床の場では、患部の腫瘍が周辺組織に浸透し腫瘍組織と正常組織の境界が不明瞭な場合、通常は腫瘍組織の完全除去を優先し、疑わしき部分を含めて切除する方法が幅広く採用されている。しかし、必要以上の切除は、望ましいものではない。特に、脳腫瘍では、不用意な切除が脳機能に対し深刻な打撃を与えかねないので、積極的な治療が困難であった。
【0003】
そこで、脳腫瘍の治療においては、次のような正常組織と識別して必要十分な部分だけを切除する脳外科手術の試みが始められている。この方法では、まず、腫瘍集積性のある蛍光物質を患者に投与し、腫瘍部への集積が進んだ段階で、無影灯や手術室内の照明を全て消した状態のまま、その蛍光物質を励起できる波長の光、例えば近紫外線等のみを患部及びその周辺に照射する。このとき、近紫外線等の照射により蛍光を放射する領域(蛍光物質の集積が進んだ領域)が腫瘍(患部)領域であるという特性を利用して、その腫瘍領域を正常組織から識別できるように可視化し、その情報を画像として記録する。その後で、通常照明に戻し、その情報に基づいて術者の脳外科手術が進められる。
【0004】
上記腫瘍集積性のある蛍光物質の例として、蛍光色素の5−ALA(Aminolevulinic Acid)が知られている。この5−ALAを投与すると、酵素の作用によって、PorphobilinogenからProtoporphyrinogen IXに化学修飾され、これが細胞内に蓄積して蛍光を発するようになる。この現象を応用することで、上記手法による腫瘍領域の識別が可能となる。
【0005】
図5は、腫瘍集積性蛍光物質として上記5−ALAを用いた従来例の腫瘍境界識別装置を示す。ここで、上記5−ALAは、生体内で自然に生成されている物質と考えられ、人体に対する副作用は小さく、経口または静注のいずれでも可能である。この5−ALAは、体内に取り込まれると、細胞内ではポルフィリン(Protoporphyrinogen IX)の濃度が上昇する。このポルフィリンを励起させる励起光の波長領域は、370nm〜380nmで、その波長領域の励起光照射によりポルフィリンから放射される蛍光の波長領域のピークは、620nm付近であることが知られている。この5−ALAの蛍光波長は赤領域であり、血液の色に近いため、肉眼での視認が困難なことが多い。
【0006】
そこで、図5に示す従来例の腫瘍境界識別装置は、励起光を発する光源部と、その励起光照射で発生する蛍光を検出するカメラ部とを備え、光源部に励起波長のみを通過させる光学フィルタを、カメラ部に蛍光波長のみを通過させる光学フィルタをそれぞれ配置した構造となっている。
【0007】
具体的には、図5に示す従来例では、通常照明灯100及び無影灯110が置かれた手術室内で、手術台上の患者PSに対し脳腫瘍(患部)の治療のために脳外科手術を施す場合を想定している。
【0008】
この脳外科手術で使用される従来例の脳腫瘍識別装置は、図示の如く、5−ALAが投与された患者PSの患部周辺に対しその細胞内に集積する蛍光物質(ポルフィリン)を励起させるための励起波長の光(近紫外線等)を照射する励起光源120と、この励起光照射により腫瘍領域に集積した蛍光物質から放射される蛍光の分布を示す画像(以下、蛍光画像)と通常の可視光による画像(以下、可視光画像)を撮像する撮像装置130と、励起光源120及び撮像装置130の動作を制御するコントロール装置140と、撮像装置130で得られる蛍光画像及び可視光画像を重畳表示又は1つの画面を2分して個別に表示する2画面表示等の画像処理を行なう画像合成装置150と、画像合成装置150で画像処理が施された画像を表示する表示装置160とを備えている。
【0009】
この内、励起光源120は、励起波長の光のみを患部近傍に照射するために、光源本体121内に設けたハロゲンランプ、メタルハライドランプ等の白色光源122からの白色光をその光路上に設けたレンズ系123及び光学フィルタ124を介して上記励起波長の光とし、その励起光を光源本体121の外部に延びて取り付けた光ファイバ125を介して患者PSの患部近傍の所定位置に誘導し、その光ファイバ125の先端部に取り付けた集光レンズ126を介してその患部付近に向けて照射する構造をもつ。
【0010】
撮像装置130は、例えばスタンド型の装置本体131内に、同じ視点から患者PSの患部近傍を撮影できるように、2種類のカメラ、すなわち可視光の波長領域に感度を持つCCD(電荷結合素子)カメラ等の可視光用カメラ132と、蛍光物質が放射する蛍光の波長領域に感度を持つCCDカメラ又は光学フィルタ付きCCDカメラ等の蛍光用カメラ133とを配置し、両カメラ132、133をその前面側に設けた機械的な可動式ミラーやハーフミラー等の切り替え用ミラー134を介して互いに切り替え可能な構造をもつ。なお、同じ視点からの画像でなくても良い場合は、上記2種のカメラ132、133がほぼ同じ患部領域を見込むように配置し、この場合に撮像装置130で得られる蛍光画像及び可視光画像は厳密には重ならないので、表示装置上に重畳表示ではなく、2画面表示で個別に表示される。
【0011】
上記の従来例の脳腫瘍識別装置によれば、まず、手術室内の室内照明灯100及び無影灯110を消灯し、励起光源120を点灯した状態で、患者PSに投与された腫瘍集積性蛍光物質である5−ALAの分布を示す患部近傍の画像(以下、蛍光画像)を撮像装置120の蛍光用カメラ133により撮像し、画像合成装置150に録画する。
【0012】
次いで、励起光源120を消灯し、室内照明灯100を点灯し、通常の可視光のもとで映し出される患部近傍の画像を撮像装置120の可視光用カメラ132により撮像し、リアルタイムで表示装置160上に表示する。このとき、表示装置160上には、術者の要求に従って上記で録画された5−ALAの分布を示す画像が、可視光で得られる画像上に重畳表示され、或は2画面表示により可視光画像と共にその参考画像として表示される。
【0013】
これらの表示画像を参照しながら、術者は必要十分な患部のみを切除する。この切除により患部に変形が生じた場合は、上述の蛍光画像の撮影→可視光画像の撮影→重畳表示又は2画面表示のサイクルを細かく繰り返すことにより、手術が進められる。
【0014】
【発明が解決しようとする課題】
しかしながら、上述した従来例の脳腫瘍識別装置では、室内照明灯の点灯/消灯と、励起光源の消灯/点灯を手術毎に繰り返し実施する必要があり、腫瘍領域の全体像が把握できる利点があるものの、煩雑な作業が発生するといった問題がある。
【0015】
すなわち、上述した従来例の方法は、腫瘍の全領域を可視化するには向いているが、外科手術を進めるには、どうしてもいちいち無影灯等、通常照明に戻さねばならず、手術を進めるために患部の変形が進むので、この手順を繰り返さねばならないといった煩わしさが存在した。
【0016】
この腫瘍領域を手術を活かすには、近紫外線照明下で蛍光を発する患部をその蛍光波長に感度をもつCCDカメラなどで一旦撮影及び記録し、その静止画像を通常照明に戻した段階で可視光領域に感度をもつCCDカメラで撮影している動画に重畳表示するといった方法が採用されている。しかし、手術が進むと、患部の変形が生じるので、この手順を頻繁に繰り返す必要があり、装置の複雑化と共に作業の複雑化を招いていた。
【0017】
本発明は、このような従来の事情を考慮してなされたもので、外科手術の手順を邪魔することなく、かつ、腫瘍領域を正確に識別しながら、より安全に腫瘍切除を行なえるように支援することを目的とする。
【0018】
【課題を解決するための手段】
上記目的を達成するため、本発明では、蛍光物質集積性腫瘍の境界識別装置として、例えば、任意の時間だけ点灯可能な仕組み、例えば機械的シャッター等を有し、且つ、腫瘍集積性のある蛍光物質を励起する波長の光を発光する光源と、その光源からの光を患部に照射したときに蛍光物質から放射される蛍光を検出する検出部と、この検出部に前記蛍光物質からの蛍光を導く光ファイバと、励起された場合と励起されない場合に対応付けて検出された蛍光の強度情報及び励起光源の強度の情報から腫瘍に集積された蛍光物質の濃度に対応するパラメータを推定する演算手段と、その結果を術者に知らせるための表示手段とを備えた構成に着目した。
【0019】
この構成においては、術者が腫瘍と正常組織との境界を判定した時点で、その境界線をマーキングするための染料塗布手段を備えることも可能である。また、光ファイバの開口部から患部表面までの間の距離を一定に保ち、且つ、患部表面を傷つけないための保護手段を光ファイバの先端部に設けることも可能である。この保護手段は、染料塗布手段のノズルの噴射口や、不要な液体を吸引除去する際に使用される吸引手段のノズルの吸引口を兼ね備えることができる。
【0020】
また、本発明では、蛍光物質集積性腫瘍の境界識別装置として、例えば、任意のタイミングで点灯/消灯をコントロールし、且つ、蛍光物質を励起する波長領域の光を発する励起光源と、その励起光源の強度を時間的に安定化させるための制御手段と、患部から放射される蛍光から特定波長を分離しその強度を検出する検出手段、例えば、光学フィルタや回折格子等と、フォトダイオード等の受光センサを組み合わせたものと、励起光源からの励起光を患部表面まで導き、且つ、患部から放射される蛍光を検出手段まで導く光ファイバと、励起光源を点灯した場合と消灯した場合とのそれぞれで検出手段により検出される蛍光強度の情報から所定の演算を行ないその演算結果を表示する演算・表示手段とを備えた構成に着目した。
【0021】
この構成においては、さらに光ファイバ開口部近傍に、患部を傷つけないように保護する手段と、患部に染料を塗布してマーキングを施すための染料塗布手段と、不要な液体を除去するための吸引器とを付加することもできる。
【0022】
この構成によれば、通常照明下でも、一定の距離を保って光ファイバの線端部(開口部)を患者表面に押し当てれば、その患部表面での蛍光物質濃度を反映した情報が簡単に得られ、染料塗布手段を使用すれば、その境界が何処にあるかの情報を簡単に可視化できるようになる。
【0023】
本発明に係る蛍光物質集積性腫瘍の境界識別装置は、このような着想をもとに完成されたものである。
【0024】
すなわち、本発明に係る蛍光物質集積性腫瘍の境界識別装置は、被検体の生体内の患部に集積して化学修飾を受けた蛍光物質に対し所定波長成分の励起光を照射し且つその点灯及び消灯の繰り返しにより前記蛍光物質の励起を断続的に行なう光源と、前記光源からの励起光を前記生体内の患部近傍に導く導光手段と、前記患部に集積した蛍光物質から放射される蛍光の強度を検出する検出手段と、前記検出手段により検出された前記光源の点灯及び消灯に対応する蛍光強度に基づいて前記蛍光物質の濃度を推定する演算手段と、前記演算手段による前記蛍光物質の濃度推定値を表示する表示手段とを備えたことを特徴とする。
【0025】
本発明において、前記光源は、機械式シャッターと特定の波長近傍成分をもつ光を透過する光学フィルタとを有するハロゲンランプ光源又はメタルハライドランプ光源、又は、前記光源の点灯及び消灯の応答性に優れたLED(発光ダイオード)或はそのLEDに光学フィルタを設けて構成されることが好適である。
【0026】
また、前記導光手段は、前記蛍光物質が集積する患部に前記励起光を導くと共に、その励起光により当該蛍光物質から放射される蛍光を前記検出手段に導く光ファイバを備えることができる。この場合、光ファイバの先端部(開口部)に励起光の分散防止及び直進性確保のために集光用のマイクロレンズを設けることが好ましい。さらに、光ファイバの先端部は、ハンドピースで構成されることがより好ましい。
【0027】
また、前記検出手段は、凹型の回折格子、凸型の回折格子、又はレンズを組み合わせてなる回折格子と、光を電気信号に変換する光検出器とから構成されることが好適である。この場合には、光源の断続的点灯及び消灯に十分に速く応答できる特性をもつことが好ましい。
【0028】
また、前記演算手段は、前記光源の点灯時における前記励起光の強度に対応する第1の波長における測定値をLonとし、前記光源の消灯時における励起光の強度に対応する第1の波長における測定値をLoffとし、前記光源の点灯時に前記検出手段により検出される蛍光の強度に対応する第1の波長と異なる第2の波長における測定値をlonとし、前記光源の消灯時に前記検出手段により検出される蛍光の強度に対応する第1の波長と異なる第2の波長における測定値をloffとし、前記蛍光物質の濃度に対応するパラメータをPとしたときの当該パラメータP=(lon−loff)/(Lon−Loff)、又は、そのパラメータPの変化に対し単調増加又はこのパラメータPと単調減少の関係にある数値を演算するものであることが好ましい。これによれば、外乱光が存在しても蛍光物質の濃度にほぼ比例するパラメータを推定することが可能になる。
【0029】
また、本発明においては、前記演算手段により推定される前記患部表面に染料を塗布してマーキングを施すための開口部を有する染料塗布手段と、前記患部表面の液体を吸引除去する開口部を有する吸引手段とをさらに備え、前記染料塗布手段の開口部及び前記吸引手段の開口部が前記光ファイバの先端部近傍の所定位置に配置されることが好ましい。この場合の光ファイバの先端部は、ハンドピースで構成されることがより好ましい。
【0030】
また、本発明においては、前記光ファイバの先端部に着脱自在で、且つ、緩やかに湾曲した形状をもつ保護手段をさらに備えることが好ましい。これによって、光ファイバの先端部を患部表面に接触させた場合にその圧力集中によって患部が傷つかないようにすることができる。
【0031】
【発明の実施の形態】
以下、本発明に係る蛍光物質集積性腫瘍の境界識別装置の実施の形態を添付図面を参照して説明する。
【0032】
図1に示す蛍光物質集積性腫瘍の境界識別装置は、通常照明灯100及び無影灯110が設置された手術室内で、患者PSの患部(脳腫瘍等の腫瘍)OBを切除する外科手術を行なう際に、例えば前述した腫瘍集積性のある蛍光色素(5−ALA等)が投与された患者PSの患部OB周辺に対し、その腫瘍細胞内に選択的に集積していく特性をもつ蛍光物質(ポルフィリン)を励起させるための励起波長の光(例えば、波長370nm〜380nmの近紫外線)を照射し、その波長領域の励起光照射によりポルフィリンから放射される所定波長領域の蛍光(例えば、波長のピークが620nm付近の近赤外線)を検出することにより、腫瘍組織と正常組織の境界を識別する装置に適用されるものである。
【0033】
すなわち、この装置は、その境界識別装置本体(以下、「装置本体」)1内に搭載される励起光発生用の光源部(例えば、近紫外線光源)2、蛍光検出用の検出部(例えば、近赤外線検出器)3、演算装置4、表示装置5、染料塗布装置6、吸引装置7及びその廃液タンク7aと、装置本体1の外部から患者PSの患部OB周辺の位置に延びて配置され、光源部2及び検出部3に接続される光ファイバ8と、染料塗布装置6に接続されるノズル6a及び吸引装置7に接続されるノズル7aと、光ファイバ8の先端部(開口部)及び両ノズル6a、7aの先端部(開口部)に設置される患部表面保護装置9とを備える。
【0034】
この内、光ファイバ8の先端部は、染料塗布装置6のノズル6a、吸引装置7のノズル7a、及び患部表面保護装置9と共に互いに一体化され、術者が手で持ちやすい形状を有するハンドピース型検出器(以下、「ハンドピース」)10を構成している。
【0035】
光源部2は、例えば制御されたタイミングで点灯/消灯を繰り返すことにより断続的に白色光を発生する励起光源21と、この白色光の波長成分の内、特定の波長近傍領域(例えば、近紫外領域)のみを通過させ、励起光として光ファイバ8に出射する光学フィルタ22とを組み合わせて構成される。
【0036】
この内、励起光源21には、例えば制御されたタイミングでその開口を開閉自在の機械的シャッターを備えたハロゲンランプ又はメタルハライドランプ等の白色光源が適用される。これに限らず、例えば波長が励起光と一致し、且つ、波長領域が狭い特性をもつLEDや半導体レーザ等の光半導体も適用可能である。
【0037】
この励起光源21の点灯/消灯のタイミングは、同期が取れるように図示しないコントローラにより制御される。この制御は、後述の演算装置4が兼用してもよい。この光源部2から断続的に発生される励起光は、光ファイバ8に送られる。
【0038】
光ファイバ8は、光源部2からの励起光及び患者PSの患部OB内に集積する蛍光物質から放射される蛍光を通過可能で、且つ、吸収しない石英ガラス又はフッ素樹脂等の材質で構成される。この光ファイバ8は、光源部2からの励起光を、その先端部の発光側開口部を介して患者PSの患部表面SFまで導き、且つ、腫瘍内の蛍光物質から放射される蛍光を、その先端部の受光側開口部を介して検出部3まで導く。
【0039】
この光ファイバ8内の発光側開口部と受光側開口部の配置例を図2に示す。図2の例では、この光ファイバ8は、そのシース8c内に、1つの受光側開口部8bがその中心位置に、また複数の発光側開口部8a…8aがその受光側開口部8bの半径方向外側の円周位置に一定間隔で、それぞれ配置されている。
【0040】
検出部3は、例えば患部OB内に集積する蛍光物質から放射される蛍光の波長成分の内、特定の波長帯域のみの強度を分離及び測定して電気信号に変換する分光測定装置が適用される。この分光測定装置は、例えば凸型回折格子、レンズと回折格子、光学フィルタ等とフォトダイオード、CCD等とを組み合わせた検出器から構成される。この検出部3により検出された患部OB付近の蛍光強度の検出値に対応する電気信号は、演算装置4に送られる。
【0041】
演算装置4は、例えばPC(パーソナル・コンピュータ)等の処理装置で構成され、検出部3により検出された蛍光強度に対応する電気信号をデジタル信号に変換し、通常照明灯100及び無影灯110等の外乱光による影響をキャンセルアウトし、蛍光物質由来の蛍光強度成分のみを推定及び計算する所定の演算処理を実行する。
【0042】
この演算処理では、例えば励起光源21の点灯時の光源強度に対応しかつ上記蛍光物質に影響されない第1の波長で測った測定値Lonと、そのときに検出される蛍光強度に対応する第1の波長で測った測定値lonと、及び励起光源21の消灯時の光源強度に対応する第1の波長と異なる第2の波長で測った測定値Loffと、そのときに検出される蛍光強度に対応する第2の波長で測った測定値loffとから、蛍光物質の濃度に対応するパラメータPとして、P=(lon−loff)/(Lon−Loff)、又はこのパラメータPと単調増加もしくは単調減少の関係にある数値を計算する。この数値は、測定誤差を減らすため、加算平均する等の統計処理を加えてもよい。
【0043】
表示装置5は、例えばCRTや液晶装置等で構成され、演算装置4による演算結果を数字、グラフ表示、疑似カラー表示等で視覚的に表示する。
【0044】
染料塗布装置6は、所定位置に生体組織用染料を塗布するためのノズル6aを備え、術者により表示装置5上の演算結果が確認され、患部表面SF上の患部OB(腫瘍組織)と正常組織との境界位置が判断されると、その患部表面SF上の境界位置に向けてそのノズル6aの開口部から生体組織用染料を塗布していき、これによりマーキング(記録)するものである。ここで用いる生体組織用染料には、例えば生体安全性が確保され、患部表面SFを染色し、血液等と視覚的に識別可能な色を有し上記蛍光物質の発光に影響を与えないものが望ましい。
【0045】
吸引装置7は、患部表面SFに存在する液体を吸引して除去するための開口部を有するノズル7aを備え、このノズル7aにより術者が必要なときだけ患部表面SF近傍の存在する体液等を除去し、それを廃液タンク7bに貯留する。
【0046】
患部表面保護装置9は、例えば滅菌され、弾力性があり、概略形状が球形のプラスチック製で、且つ、ハンドピース10を成す光ファイバ8の先端部、染料塗布装置6のノズル6a、及び吸引装置7のノズル7aを適切な位置に配置できる構造を持つものが好ましい。この患部表面保護装置9により、光ファイバ8の先端部、及び上記2つのノズル6a、7aにより患部表面SFが傷つかないように保護される。
【0047】
ここで、本実施形態の作用を説明する。
【0048】
まず、患者PSの患部OB切除の外科手術に際し、患者PSに腫瘍集積性のある蛍光色素(5−ALA等)を投与し、ハンドピース10の先端部を患者PSの生体組織に軽く押し当てた状態で、明らかに正常組織と見られる部分と、明らかに腫瘍部と見られる部分とのそれぞれで、通常照明灯100及び無影灯110を点灯した状態で、前述した蛍光物質集積性腫瘍の境界識別装置による測定を実施する。
【0049】
この測定実施に際し、光源部2からの励起光が断続的に光ファイバ8を介して患者PSの生体組織に照射され、その生体組織からの蛍光強度が光ファイバ8を介して検出部3にて検出され、その検出信号が演算部4に出力される。
【0050】
これにより、演算部4は、通常照明灯100及び無影灯110の点灯時の外乱光による影響をキャンセルアウトすることにより、蛍光物質由来の蛍光強度成分のみを上記パラメータを求める計算式等により推定・計算し、その値を記録しておく。また、過去の臨床経験値から、腫瘍組織かどうかを判定するための閾値を求めておく。
【0051】
これにより、無影灯110や通常照明灯100による照明がある場合でも、ハンドピース10内の光ファイバ8の先端部を介して近紫外線等の励起光の露光範囲を限局できるため、励起光を照射した場合とそうでない場合との蛍光波長の強度変化データから、蛍光物質の集積濃度を定量的に推定することが可能となるこのデータから腫瘍の境界部分をリアルタイムに識別できるので、判定した時点で生体組織用染料を塗布すれば、その境界部分を可視化できる。
【0052】
そこで、術者は、ハンドピース10の先端部を患者PSの生体組織に軽く押し当てて、上記測定を行ないながら、その測定値と上記判定基準となる閾値とに基づいて、患部表面SF上の腫瘍組織と正常組織との境界位置を識別し、これで識別された患部表面SF上の境界位置に染料塗布装置6によりマーキングを施していく。これにより、必要な領域のマーキングが完了すると、この段階で外科的な切除を行なう。さらに手術を進める場合は、必要十分な部分を除去するまで、同様のマーキング→切除のサイクルを繰り返し行なう。
【0053】
従って、本実施形態によれば、無影灯や通常照明灯等が点灯していても、蛍光色素の集積した腫瘍領域を定量的に識別しその境界情報を脳表面等の患部表面にマーキング(記録)し、そのままの照明条件下で脳外科手術を進めることができる。すなわち、無影灯等を点灯していても、患部(腫瘍)の境界部位を明瞭に描出でき、それをもとに必要最小限の患部のみをより安全に切除できるようになる。また、生体組織用染料によるマーキングは、それ自体は比較的ローテクなものではあるが、生体組織表面を直接染めるため、切除により変形が生じても従来の重畳表示とは異なり、変形に追従して境界を表示し続けるといった利点もある。
【0054】
なお、上記実施形態の光ファイバ8には、その先端部に励起光の分散防止及びその直進性確保のために集光用マイクロレンズを設けてもよい。また、本発明の導光手段は、上記光ファイバ8に限らず、レーザーメスのようなミラーを応用した導光手段を用いることも可能である。
【0055】
また、本実施形態のハンドピース10は、光ファイバ8の先端部、染料塗布装置6のノズル6a、吸引装置7のノズル7a、患部表面保護装置9を一体化でき、術者が手で持ちやすい形状を持つものであれば、いずれのタイプでも適用可能である。このハンドピース10の具体例を図3及び図4に示す。
【0056】
図3に示すハンドピース10は、手で握りやすいペン型(棒状)の筒状本体内に光ファイバ8の先端部、染料塗布装置6のノズル6a、吸引装置7のノズル7a、患部表面保護装置9を一体化したもので、その本体外側表面上の適宜位置に2つの手元スイッチS1(蛍光測定のコントロール用)及びS2(染料塗布用)が設けられている。
【0057】
このハンドピース100内において、光ファイバ8の開口部は必ずしも患部に接触している必要はないが、もしその開口部と患部表面SFとの間の距離が変化すると、その距離に応じて測定中の蛍光強度が変化すれば、蛍光物質の濃度を誤って推定してしまう危険性がある。
【0058】
そこで、図4に示すように、光ファイバ8の開口部先端面10aと、患部表面SFとの間の距離関係を一定に保ち(図中のD参照)、且つ、患部表面SFを細い光ファイバ8やノズル6a、7aで傷つけないようにするため、柔らかく滅菌可能で生体安全性が確保された樹脂を成形した患部表面保護装置9をハンドピース10の先端部に取り付けておく。この患部表面保護装置9の形状としては、生体組織との引っかかり等の観点から概略球状のものが好ましい。
【0059】
ここで、本変形例の作用を説明すると、患部表面保護装置9を患部表面SFに押し当てた状態で、手元スイッチS1を押し、蛍光物質の濃度に対応するパラメータを測定する。この場合、手元スイッチS1は、押しつづけている間だけ測定するものであってもよいし、1回目押した時点で測定が開始され、2回目で測定がストップするものであってもよい。
【0060】
ここで、比較パラメータとして、明らかに腫瘍とみなし得る部分のパラメータP1と、明らかに正常とみなせる部分のパラメータP2を予め装置内に登録しておき、関心位置でのパラメータP3を測定する。例えば、P1を100%、P2を0%に換算し、そのパーセンテージ100×(P3−P2)/(P1−P2)か、もしくはそれと単調増加もしくは単調減少の関係にある数値、又は図形で表示する。
【0061】
そして、上記測定値に基づいて、術者が腫瘍組織と正常組織との境界を判断し、境界と判断した位置にハンドピース10上の染料塗布用の手元スイッチS2を押し、染料塗布装置6のノズル6aを介して染料を塗布する。この手順を繰り返し行ない、腫瘍領域を囲むようにマーキングを施す。
【0062】
このマーキングが終了した段階で、マーキングされた腫瘍領域に対する外科的切除を実施する。ある程度切除が進むと、患部が変形したり、マーキングを含めて切除したりするので、その時点でマーキングの作業を繰り返す。これによって、切除が必要な部位を必要且つ十分な領域だけに限定して安全に切除することができる。
【0063】
なお、本発明は、代表的に例示した上述の実施形態に限定されるものではなく、当業者であれば、特許請求の範囲の記載内容に基づき、その要旨を逸脱しない範囲内で種々の態様に変形、変更することができる。これらの変更、変形例も本発明の権利範囲に属するものである。
【0064】
【発明の効果】
以上説明したように、本発明によれば、腫瘍集積性蛍光物質を用いた腫瘍境界識別の際に、通常照明下のままで定量的に正常組織との識別、及び境界のマーキングを簡単な装置構成で可能になる。これによって、外科手術の手順を邪魔することなく、かつ、腫瘍領域を正確に識別しながら安全に腫瘍切除等を行なうことができる。
【図面の簡単な説明】
【図1】本発明の実施形態に係る蛍光物質集積性腫瘍の境界識別装置の全体構成を示す概略ブロック図。
【図2】光ファイバの受光側開口部と発光側開口部の配置例を示す模式的断面図。
【図3】変形例のハンドピースの構造を説明する図。
【図4】ハンドピース先端側に配置される患部表面保護装置の機能を説明する図。
【図5】従来例の脳腫瘍識別装置の全体構成を示す概略ブロック図。
【符号の説明】
1 装置本体
2 光源部
3 検出部
4 演算装置
5 表示装置
6 染料塗布装置
6a ノズル(染料塗布装置)
7 吸引装置
7a ノズル(吸引装置)
7b 廃液タンク
8 光ファイバ
9 保護装置
10 ハンドピース
21 励起光源
22 光学フィルタ
100 無影灯
110 通常照明灯
PS 患者
OB 患部
SF 患部表面
[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an apparatus for identifying a boundary of a fluorescent substance-accumulating tumor, and particularly, when performing an operation of surgically resecting a tumor having a fluorescent substance-accumulating property, the boundary of the tumor is illuminated by an operating light or a normal light. However, the present invention relates to an assisting device for assisting a surgical operation for tumor resection by detecting without being affected by the influence and marking the boundary surface thereof. This support device can be used for, for example, brain surgery or general surgery in which the boundary between tumor tissue and normal tissue is very important.
[0002]
[Prior art]
In clinical settings, when the tumor in the affected area has penetrated into the surrounding tissue and the boundary between the tumor tissue and normal tissue is unclear, it is usually a priority to completely remove the tumor tissue, and the resection method including the suspected part is widely adopted. ing. However, unnecessary resection is not desirable. Especially in brain tumors, aggressive treatment was difficult because careless resection could severely damage brain function.
[0003]
Therefore, in the treatment of brain tumors, attempts have been made for brain surgery in which the following normal tissue is identified and only necessary and sufficient portions are excised. In this method, first, a fluorescent substance with tumor accumulation is administered to the patient, and when the accumulation in the tumor has progressed, the fluorescent substance is removed while all operating lights and operating room lighting are turned off. Light of a wavelength that can be excited, for example, only near-ultraviolet light, etc., is applied to the affected area and its surroundings. At this time, by utilizing the characteristic that a region that emits fluorescence by irradiation with near ultraviolet rays (a region where the accumulation of the fluorescent substance is advanced) is a tumor (affected part) region, the tumor region can be distinguished from normal tissue. Visualize and record the information as an image. Thereafter, the lighting is returned to the normal lighting, and the brain surgery of the operator is performed based on the information.
[0004]
As an example of the above-mentioned fluorescent substance having a tumor accumulation property, a fluorescent dye 5-ALA (Aminolevulinic Acid) is known. When 5-ALA is administered, Porphobilinogen is chemically modified to Protoporphyrogenogen IX by the action of an enzyme, which accumulates in cells and emits fluorescence. By applying this phenomenon, it is possible to identify a tumor region by the above method.
[0005]
FIG. 5 shows a conventional tumor boundary discriminating apparatus using 5-ALA as the tumor-accumulating fluorescent substance. Here, the 5-ALA is considered to be a substance naturally generated in a living body, has a small side effect on the human body, and can be administered either orally or intravenously. When 5-ALA is taken into the body, the concentration of porphyrin (Protoporphyrinogen IX) in the cells increases. It is known that the wavelength region of the excitation light for exciting the porphyrin is 370 nm to 380 nm, and the peak of the wavelength region of the fluorescence emitted from the porphyrin by irradiation of the excitation light in the wavelength region is around 620 nm. Since the fluorescence wavelength of this 5-ALA is in the red region and is close to the color of blood, it is often difficult to visually recognize it with the naked eye.
[0006]
Therefore, the conventional tumor boundary identifying apparatus shown in FIG. 5 includes a light source unit that emits excitation light, and a camera unit that detects fluorescence generated by the irradiation of the excitation light, and the light source unit transmits only the excitation wavelength. The filter has a structure in which an optical filter that allows only a fluorescence wavelength to pass is arranged in a camera unit.
[0007]
Specifically, in the conventional example shown in FIG. 5, brain surgery is performed on a patient PS on an operating table to treat a brain tumor (affected area) in an operating room where a normal illumination light 100 and an operating light 110 are placed. It is assumed that it is applied.
[0008]
As shown in the figure, a conventional brain tumor identification apparatus used in this brain surgery performs an excitation for exciting a fluorescent substance (porphyrin) that accumulates in cells around the affected part of a patient PS to which 5-ALA has been administered. An excitation light source 120 for irradiating light of a wavelength (such as near-ultraviolet light), an image (hereinafter, a fluorescent image) showing the distribution of fluorescence emitted from a fluorescent substance accumulated in a tumor region by this excitation light irradiation, and normal visible light An imaging device 130 that captures an image (hereinafter, a visible light image); a control device 140 that controls the operation of the excitation light source 120 and the imaging device 130; and a fluorescent image and a visible light image obtained by the imaging device 130 that are superimposed or displayed. An image synthesizing device 150 that performs image processing such as two-screen display in which one screen is divided into two and individually displayed, and an image processed by the image synthesizing device 150 is displayed. And a display device 160.
[0009]
Among them, the excitation light source 120 provided white light from a white light source 122 such as a halogen lamp or a metal halide lamp provided in the light source main body 121 on its optical path in order to irradiate only the light of the excitation wavelength to the vicinity of the affected part. The light having the above-described excitation wavelength is passed through the lens system 123 and the optical filter 124, and the excitation light is guided to a predetermined position near the affected part of the patient PS via an optical fiber 125 extending and attached to the outside of the light source main body 121. It has a structure of irradiating near the affected part through a condenser lens 126 attached to the tip of the optical fiber 125.
[0010]
The imaging device 130 has two types of cameras, for example, a CCD (charge coupled device) having sensitivity in the visible light wavelength region, so that the vicinity of the affected part of the patient PS can be imaged from the same viewpoint in a stand-type device main body 131, for example. A camera 132 for visible light, such as a camera, and a camera 133 for fluorescence, such as a CCD camera or a CCD camera with an optical filter, having sensitivity in the wavelength region of the fluorescent light emitted by the fluorescent substance are arranged. It has a structure that can be switched between each other via a switching mirror 134 such as a mechanical movable mirror or a half mirror provided on the side. If the images need not be viewed from the same viewpoint, the two types of cameras 132 and 133 are arranged so as to see substantially the same affected area. In this case, the fluorescence image and the visible light image obtained by the imaging device 130 are obtained. Are not strictly overlapped with each other, they are displayed individually on a two-screen display instead of being superimposed on the display device.
[0011]
According to the above-described conventional brain tumor identification apparatus, first, the tumor-integrating fluorescent substance administered to the patient PS in a state where the interior lighting lamp 100 and the surgical light 110 in the operating room are turned off and the excitation light source 120 is turned on. An image near the affected part (hereinafter, a fluorescent image) showing the distribution of 5-ALA is captured by the fluorescent camera 133 of the imaging device 120 and recorded in the image synthesizing device 150.
[0012]
Next, the excitation light source 120 is turned off, the indoor lighting lamp 100 is turned on, an image of the vicinity of the affected part, which is projected under normal visible light, is captured by the visible light camera 132 of the imaging device 120, and the display device 160 is displayed in real time. Display above. At this time, the image showing the distribution of 5-ALA recorded above according to the operator's request is superimposed on the image obtained by visible light on the display device 160, or the visible light is displayed by two-screen display. It is displayed together with the image as its reference image.
[0013]
The operator removes only the necessary and sufficient affected part while referring to these display images. When the affected part is deformed by this excision, the operation is advanced by finely repeating the above-described cycle of capturing the fluorescent image → capturing the visible light image → superimposed display or two-screen display.
[0014]
[Problems to be solved by the invention]
However, in the above-described conventional brain tumor identification apparatus, it is necessary to repeatedly turn on / off the indoor illumination lamp and turn off / on the excitation light source for each operation, and there is an advantage that the entire image of the tumor region can be grasped. There is a problem that complicated work occurs.
[0015]
That is, the above-described conventional method is suitable for visualizing the entire region of the tumor, but in order to proceed with the surgical operation, it is absolutely necessary to return to normal illumination, such as an operating light, and to proceed with the operation. Since the deformation of the affected part progresses, there is a trouble that this procedure must be repeated.
[0016]
In order to take advantage of surgery in this tumor area, the affected part that emits fluorescence under near-ultraviolet light is once photographed and recorded with a CCD camera or the like that is sensitive to the fluorescence wavelength, and the still image is returned to normal illumination when visible light is applied. A method of superimposing and displaying a moving image captured by a CCD camera having sensitivity in an area is adopted. However, as the operation proceeds, the affected part is deformed, so that this procedure needs to be repeated frequently, which has led to a complicated apparatus and complicated work.
[0017]
The present invention has been made in view of such a conventional situation, and has been made to enable safer tumor resection without disturbing a surgical procedure and accurately identifying a tumor region. The purpose is to support.
[0018]
[Means for Solving the Problems]
In order to achieve the above object, according to the present invention, as a boundary discriminating apparatus for a fluorescent substance-accumulating tumor, for example, a mechanism capable of lighting for an arbitrary time, for example, a mechanical shutter or the like, and a fluorescent substance having a tumor accumulating property A light source that emits light having a wavelength that excites the substance, a detection unit that detects fluorescence emitted from the fluorescent substance when the light from the light source is irradiated on the affected part, and detects fluorescence from the fluorescent substance in the detection unit. Arithmetic means for estimating a parameter corresponding to the concentration of the fluorescent substance accumulated in the tumor from the optical fiber to be guided and the intensity information of the detected fluorescence and the intensity of the excitation light source in association with the case of being excited and the case of not being excited And a display means for notifying the operator of the result.
[0019]
In this configuration, when the surgeon determines the boundary between the tumor and the normal tissue, it is also possible to provide a dye application means for marking the boundary. It is also possible to keep the distance from the opening of the optical fiber to the surface of the affected part constant and to provide a protection means at the distal end of the optical fiber for preventing the surface of the affected part from being damaged. This protection means can also serve as a nozzle orifice of a nozzle of the dye application means or a suction port of a nozzle of the suction means used for sucking and removing unnecessary liquid.
[0020]
Further, in the present invention, as a boundary discriminating device for a fluorescent substance-integrating tumor, for example, an excitation light source that controls lighting / extinguishing at an arbitrary timing and emits light in a wavelength region that excites the fluorescent substance, and the excitation light source Control means for stabilizing the intensity of light over time, and detection means for separating a specific wavelength from the fluorescence emitted from the affected part and detecting the intensity, such as an optical filter or a diffraction grating, and receiving light by a photodiode or the like. The combination of the sensor, the optical fiber that guides the excitation light from the excitation light source to the affected part surface, and guides the fluorescence emitted from the affected part to the detection means, and the case where the excitation light source is turned on and the case where the excitation light is turned off, respectively. Attention has been paid to a configuration including a calculation / display means for performing a predetermined calculation from information on the fluorescence intensity detected by the detection means and displaying the calculation result.
[0021]
In this configuration, further, in the vicinity of the optical fiber opening, means for protecting the affected part from being damaged, dye applying means for applying a dye to the affected part for marking, and suction for removing unnecessary liquid. A container can be added.
[0022]
According to this configuration, even under normal lighting, if the wire end (opening) of the optical fiber is pressed against the patient surface while maintaining a certain distance, information reflecting the fluorescent substance concentration on the affected surface can be easily obtained. The use of the dye application means makes it possible to easily visualize information on where the boundary is.
[0023]
The apparatus for identifying a boundary of a fluorescent substance-accumulating tumor according to the present invention has been completed based on such an idea.
[0024]
That is, the apparatus for identifying a boundary of a fluorescent substance-accumulating tumor according to the present invention irradiates excitation light of a predetermined wavelength component to a fluorescent substance that has been accumulated in an affected part of a living body and has undergone chemical modification, and is illuminated and turned on. A light source that intermittently excites the fluorescent substance by repeatedly turning off the light, a light guiding unit that guides the excitation light from the light source to the vicinity of the affected part in the living body, and a fluorescent light emitted from the fluorescent substance accumulated in the affected part. Detecting means for detecting the intensity; calculating means for estimating the concentration of the fluorescent substance based on the fluorescent intensity corresponding to turning on and off the light source detected by the detecting means; and the concentration of the fluorescent substance by the calculating means. Display means for displaying the estimated value.
[0025]
In the present invention, the light source is a halogen lamp light source or a metal halide lamp light source having a mechanical shutter and an optical filter that transmits light having a component near a specific wavelength, or has excellent responsiveness of turning on and off the light source. It is preferable that an LED (light emitting diode) or an optical filter is provided for the LED.
[0026]
In addition, the light guide unit may include an optical fiber that guides the excitation light to an affected area where the fluorescent substance accumulates, and guides fluorescence emitted from the fluorescent substance by the excitation light to the detection unit. In this case, it is preferable to provide a condensing microlens at the tip (opening) of the optical fiber in order to prevent the dispersion of the excitation light and ensure the straightness. Further, it is more preferable that the distal end of the optical fiber is constituted by a handpiece.
[0027]
Further, it is preferable that the detection means includes a diffraction grating formed by combining a concave diffraction grating, a convex diffraction grating, or a lens, and a photodetector that converts light into an electric signal. In this case, it is preferable to have a characteristic capable of responding quickly and intermittently to turning on and off the light source.
[0028]
Further, the calculating means sets the measured value at the first wavelength corresponding to the intensity of the excitation light when the light source is turned on to Lon, and sets the measured value at the first wavelength corresponding to the intensity of the excitation light when the light source is turned off. The measured value is Loff, the measured value at a second wavelength different from the first wavelength corresponding to the intensity of the fluorescence detected by the detecting unit when the light source is turned on is lon, and the detecting unit detects when the light source is turned off. When a measured value at a second wavelength different from the first wavelength corresponding to the intensity of the detected fluorescence is defined as loff, and a parameter corresponding to the concentration of the fluorescent substance is defined as P, the parameter P = (lon-loff) / (Lon-Loff) or a numerical value having a monotonic increase or a monotonically decreasing relationship with the parameter P with respect to a change in the parameter P. Door is preferable. According to this, it is possible to estimate a parameter that is substantially proportional to the concentration of the fluorescent substance even when disturbance light exists.
[0029]
Further, in the present invention, there is provided a dye application unit having an opening for applying a dye to the affected part surface estimated by the arithmetic unit and performing marking, and an opening for sucking and removing the liquid on the affected part surface. It is preferable that the optical fiber further includes a suction unit, and the opening of the dye application unit and the opening of the suction unit are arranged at predetermined positions near the tip of the optical fiber. In this case, the tip of the optical fiber is more preferably constituted by a handpiece.
[0030]
Further, in the present invention, it is preferable that the optical fiber further comprises a protection means which is detachably attached to the distal end portion of the optical fiber and has a gently curved shape. Thus, when the distal end portion of the optical fiber is brought into contact with the surface of the affected part, it is possible to prevent the affected part from being damaged by the pressure concentration.
[0031]
BEST MODE FOR CARRYING OUT THE INVENTION
An embodiment of the apparatus for identifying a boundary of a fluorescent substance-accumulating tumor according to the present invention will be described below with reference to the accompanying drawings.
[0032]
The fluorescent substance-accumulating tumor boundary discriminating apparatus shown in FIG. 1 performs a surgical operation for excision of an affected part (tumor such as a brain tumor) OB of a patient PS in an operating room where a normal illumination light 100 and an operating light 110 are installed. At this time, for example, a fluorescent substance having a property of selectively accumulating in the tumor cells around the affected part OB of the patient PS to which the above-mentioned fluorescent dye (eg, 5-ALA) having a tumor accumulating property is administered. Porphyrin) is irradiated with light having an excitation wavelength (for example, near-ultraviolet light having a wavelength of 370 nm to 380 nm) to excite the porphyrin, and fluorescence (for example, a wavelength peak) emitted from the porphyrin by irradiation of the excitation light in that wavelength region. Is applied to a device for identifying the boundary between tumor tissue and normal tissue by detecting near-infrared light near 620 nm.
[0033]
That is, this device includes a light source unit (for example, near-ultraviolet light source) 2 for generating excitation light and a detection unit (for example, for detecting fluorescence) mounted in a boundary identification device main body (hereinafter, “device main body”) 1. A near-infrared detector 3, a computing device 4, a display device 5, a dye coating device 6, a suction device 7 and a waste liquid tank 7 a thereof, and a device extending from the outside of the device body 1 to a position around the affected part OB of the patient PS, An optical fiber 8 connected to the light source unit 2 and the detecting unit 3; a nozzle 6a connected to the dye coating device 6 and a nozzle 7a connected to the suction device 7; An affected-part surface protection device 9 is provided at the distal ends (openings) of the nozzles 6a and 7a.
[0034]
Of these, the tip of the optical fiber 8 is integrated with the nozzle 6a of the dye coating device 6, the nozzle 7a of the suction device 7, and the diseased part surface protection device 9, and is a handpiece having a shape that is easy for the operator to hold by hand. The mold detector (hereinafter, “handpiece”) 10 is configured.
[0035]
The light source unit 2 includes, for example, an excitation light source 21 that generates white light intermittently by repeatedly turning on and off at a controlled timing, and an area near a specific wavelength (for example, near ultraviolet) among the wavelength components of the white light. ), And an optical filter 22 that emits excitation light to the optical fiber 8 as excitation light.
[0036]
Among them, as the excitation light source 21, for example, a white light source such as a halogen lamp or a metal halide lamp having a mechanical shutter whose opening can be freely opened and closed at a controlled timing is applied. However, the present invention is not limited to this. For example, an optical semiconductor such as an LED or a semiconductor laser having a characteristic in which the wavelength matches the excitation light and has a narrow wavelength range is also applicable.
[0037]
The timing of turning on / off the excitation light source 21 is controlled by a controller (not shown) so as to be synchronized. This control may be shared by the arithmetic unit 4 described later. The excitation light generated intermittently from the light source unit 2 is sent to the optical fiber 8.
[0038]
The optical fiber 8 is made of a material such as quartz glass or fluororesin that can pass the excitation light from the light source unit 2 and the fluorescent light emitted from the fluorescent material accumulated in the affected part OB of the patient PS and does not absorb the light. . The optical fiber 8 guides the excitation light from the light source unit 2 to the diseased part surface SF of the patient PS through the light emitting side opening at the distal end thereof, and emits the fluorescence emitted from the fluorescent substance in the tumor. It is guided to the detection unit 3 through the light receiving side opening at the tip.
[0039]
FIG. 2 shows an arrangement example of the light-emitting side opening and the light-receiving side opening in the optical fiber 8. In the example of FIG. 2, the optical fiber 8 has a light receiving side opening 8b at its center position in a sheath 8c thereof, and a plurality of light emitting side openings 8a... 8a having a radius of the light receiving side opening 8b. They are arranged at regular intervals at circumferential positions outside in the direction.
[0040]
As the detection unit 3, for example, a spectrometer that separates and measures the intensity of only a specific wavelength band among the wavelength components of the fluorescence emitted from the fluorescent substance accumulated in the affected area OB and converts the intensity into an electric signal is applied. . This spectrometer includes, for example, a detector in which a convex diffraction grating, a lens and a diffraction grating, an optical filter and the like, a photodiode, a CCD, and the like are combined. The electric signal corresponding to the detected value of the fluorescence intensity near the affected part OB detected by the detection unit 3 is sent to the arithmetic unit 4.
[0041]
The arithmetic unit 4 is composed of a processing device such as a personal computer (PC), for example, and converts an electric signal corresponding to the fluorescence intensity detected by the detection unit 3 into a digital signal. And the like, and cancels out the influence of disturbance light, and executes a predetermined calculation process for estimating and calculating only the fluorescence intensity component derived from the fluorescent substance.
[0042]
In this arithmetic processing, for example, a measurement value Lon corresponding to the light source intensity when the excitation light source 21 is turned on and measured at the first wavelength not affected by the fluorescent substance, and a first value corresponding to the fluorescence intensity detected at that time. And the measured value Loff measured at a second wavelength different from the first wavelength corresponding to the light source intensity when the excitation light source 21 is turned off, and the fluorescence intensity detected at that time. From the measured value loff measured at the corresponding second wavelength, P = (lon-loff) / (Lon-Loff) as a parameter P corresponding to the concentration of the fluorescent substance, or a monotonic increase or a monotonic decrease with this parameter P Is calculated. This numerical value may be subjected to statistical processing such as averaging to reduce the measurement error.
[0043]
The display device 5 is composed of, for example, a CRT, a liquid crystal device, or the like, and visually displays a calculation result by the calculation device 4 by a numeral, a graph, a pseudo color display, or the like.
[0044]
The dye application device 6 includes a nozzle 6a for applying a biological tissue dye to a predetermined position. The operator confirms the calculation result on the display device 5 and determines that the diseased part OB (tumor tissue) on the diseased part surface SF is normal. When the boundary position with the tissue is determined, the living tissue dye is applied from the opening of the nozzle 6a toward the boundary position on the diseased part surface SF, thereby performing marking (recording). Among the dyes for living tissue used herein, for example, those that ensure biosafety, stain the affected part surface SF, have a color that can be visually distinguished from blood or the like, and do not affect the emission of the fluorescent substance are used. desirable.
[0045]
The suction device 7 includes a nozzle 7a having an opening for sucking and removing a liquid existing on the affected part surface SF, and the nozzle 7a can remove a body fluid or the like existing near the affected part surface SF only when the operator needs it. It is removed and stored in the waste liquid tank 7b.
[0046]
The diseased part surface protection device 9 is made of, for example, sterilized, resilient, plastic having a substantially spherical shape, and has a distal end portion of an optical fiber 8 forming a handpiece 10, a nozzle 6a of a dye coating device 6, and a suction device. It is preferable that the nozzle 7a has a structure in which the nozzle 7a can be disposed at an appropriate position. The diseased part surface protection device 9 protects the diseased part surface SF from being damaged by the distal end portion of the optical fiber 8 and the two nozzles 6a and 7a.
[0047]
Here, the operation of the present embodiment will be described.
[0048]
First, at the time of surgical operation for resection of the affected part of the patient PS, a fluorescent dye (eg, 5-ALA) having tumor accumulation is administered to the patient PS, and the tip of the handpiece 10 is lightly pressed against the living tissue of the patient PS. In the state, in the state where the normal illumination lamp 100 and the surgical light 110 are turned on in each of the part clearly seen as a normal tissue and the part clearly seen as a tumor part, the boundary of the above-mentioned fluorescent substance accumulation tumor The measurement by the identification device is performed.
[0049]
At the time of performing this measurement, the excitation light from the light source unit 2 is intermittently applied to the living tissue of the patient PS via the optical fiber 8, and the fluorescence intensity from the living tissue is detected by the detection unit 3 via the optical fiber 8. It is detected, and the detection signal is output to the arithmetic unit 4.
[0050]
Thereby, the arithmetic unit 4 cancels out the influence of the disturbance light when the normal illumination lamp 100 and the operating light 110 are turned on, thereby estimating only the fluorescence intensity component derived from the fluorescent substance using a calculation formula or the like for obtaining the above parameters.・ Calculate and record the value. In addition, a threshold for determining whether or not the tissue is a tumor tissue is obtained from past clinical experience values.
[0051]
Thereby, even when there is illumination by the surgical light 110 or the normal illumination lamp 100, the exposure range of the excitation light such as near ultraviolet light can be limited through the tip of the optical fiber 8 in the handpiece 10, so that the excitation light is From the intensity change data of the fluorescence wavelength between the case of irradiation and the case of non-irradiation, it is possible to quantitatively estimate the concentration of accumulated fluorescent substance. From this data, the boundary part of the tumor can be identified in real time. If a dye for living tissue is applied, the boundary can be visualized.
[0052]
Therefore, the surgeon gently presses the distal end of the handpiece 10 against the living tissue of the patient PS, and performs the above-described measurement. The boundary position between the tumor tissue and the normal tissue is identified, and the boundary position on the diseased part surface SF thus identified is marked by the dye coating device 6. Thus, when the necessary area is completely marked, surgical resection is performed at this stage. When further surgery is performed, the same marking → resection cycle is repeated until a necessary and sufficient portion is removed.
[0053]
Therefore, according to the present embodiment, even when the surgical light or the normal illumination light is turned on, the tumor region where the fluorescent dye is accumulated is quantitatively identified, and the boundary information thereof is marked on the surface of the diseased part such as the brain surface. Recording) and proceed with brain surgery under the same lighting conditions. That is, even when the surgical light or the like is turned on, the boundary portion of the affected part (tumor) can be clearly drawn, and based on the boundary part, only the necessary minimum affected part can be more safely removed. In addition, although marking with a dye for living tissue is relatively low-tech in itself, it is directly dyed on the surface of living tissue, so even if deformation occurs due to excision, unlike conventional superimposed display, it follows the deformation and follows the deformation There is also the advantage of keeping the border displayed.
[0054]
Note that the optical fiber 8 of the above embodiment may be provided with a condensing microlens at the tip thereof for preventing dispersion of the excitation light and ensuring its straightness. Further, the light guide means of the present invention is not limited to the optical fiber 8, but a light guide means using a mirror such as a laser knife can be used.
[0055]
In addition, the handpiece 10 of the present embodiment can integrate the distal end of the optical fiber 8, the nozzle 6a of the dye coating device 6, the nozzle 7a of the suction device 7, and the affected part surface protection device 9, so that the operator can easily hold it by hand. Any type can be applied as long as it has a shape. A specific example of the handpiece 10 is shown in FIGS.
[0056]
The handpiece 10 shown in FIG. 3 has a pen-shaped (rod-shaped) cylindrical main body that is easy to grasp with the hand, the tip of the optical fiber 8, the nozzle 6a of the dye coating device 6, the nozzle 7a of the suction device 7, and the affected part surface protection device. 9, two hand switches S1 (for control of fluorescence measurement) and S2 (for dye application) are provided at appropriate positions on the outer surface of the main body.
[0057]
In the handpiece 100, the opening of the optical fiber 8 does not necessarily need to be in contact with the affected part, but if the distance between the opening and the affected part surface SF changes, the measurement is performed according to the distance. If the fluorescence intensity changes, the concentration of the fluorescent substance may be erroneously estimated.
[0058]
Therefore, as shown in FIG. 4, the distance relationship between the opening end surface 10a of the optical fiber 8 and the diseased part surface SF is kept constant (see D in the figure), and the diseased part surface SF is thinned. In order to prevent damage by the nozzle 8 and the nozzles 6a and 7a, the affected part surface protection device 9 made of a soft resin that can be sterilized and has biosafety secured is attached to the distal end of the handpiece 10. The shape of the diseased part surface protection device 9 is preferably a substantially spherical shape from the viewpoint of catching with a living tissue or the like.
[0059]
Here, the operation of the present modified example will be described. With the affected part surface protection device 9 pressed against the affected part surface SF, the hand switch S1 is pressed, and a parameter corresponding to the concentration of the fluorescent substance is measured. In this case, the hand switch S1 may be one that measures only while the switch is kept depressed, or one that starts measurement at the time of the first press and stops measurement at the second time.
[0060]
Here, as a comparison parameter, a parameter P1 of a portion that can be clearly regarded as a tumor and a parameter P2 of a portion that can be clearly regarded as normal are registered in the apparatus in advance, and a parameter P3 at a position of interest is measured. For example, P1 is converted to 100% and P2 is converted to 0%, and the percentage is displayed as 100 × (P3−P2) / (P1−P2), or a numerical value or a figure in a monotonically increasing or monotonically decreasing relationship therewith. .
[0061]
Then, based on the measured values, the surgeon determines the boundary between the tumor tissue and the normal tissue, pushes the hand switch S2 for dye application on the handpiece 10 to the position determined as the boundary, The dye is applied through the nozzle 6a. This procedure is repeated to make a marking around the tumor area.
[0062]
When the marking is completed, surgical resection is performed on the marked tumor region. When the excision progresses to some extent, the affected part is deformed and the excision including the marking is performed, so the marking operation is repeated at that time. As a result, it is possible to safely remove the portion that needs to be removed by limiting it to a necessary and sufficient region.
[0063]
It should be noted that the present invention is not limited to the exemplary embodiment described above as a representative, and those skilled in the art may use various modes based on the description in the claims without departing from the spirit of the invention. Can be modified and changed. These changes and modifications also fall within the scope of the present invention.
[0064]
【The invention's effect】
As described above, according to the present invention, when identifying a tumor boundary using a tumor-accumulating fluorescent substance, it is possible to quantitatively distinguish from a normal tissue and mark the boundary quantitatively under normal illumination. It becomes possible with the configuration. As a result, it is possible to safely perform tumor excision or the like without disturbing the surgical procedure and accurately identifying the tumor region.
[Brief description of the drawings]
FIG. 1 is a schematic block diagram showing the overall configuration of a device for identifying a boundary of a fluorescent substance-accumulating tumor according to an embodiment of the present invention.
FIG. 2 is a schematic cross-sectional view showing an example of arrangement of a light receiving side opening and a light emitting side opening of an optical fiber.
FIG. 3 is a diagram illustrating the structure of a handpiece according to a modification.
FIG. 4 is a view for explaining the function of an affected part surface protection device arranged on the tip side of the handpiece.
FIG. 5 is a schematic block diagram showing the overall configuration of a conventional brain tumor identification device.
[Explanation of symbols]
1 Device body
2 Light source
3 Detector
4 arithmetic unit
5 Display device
6 Dye coating device
6a nozzle (dye coating device)
7 Suction device
7a Nozzle (suction device)
7b Waste liquid tank
8 Optical fiber
9 Protective device
10 Handpiece
21 Excitation light source
22 Optical Filter
100 operating light
110 Normal lighting
PS patient
OB affected area
SF affected area surface

Claims (8)

被検体の生体内の患部に集積して化学修飾を受けた蛍光物質に対し所定波長成分の励起光を照射し且つその点灯及び消灯の繰り返しにより前記蛍光物質の励起を断続的に行なう光源と、
前記光源からの励起光を前記生体内の患部近傍に導く導光手段と、
前記患部に集積した蛍光物質から放射される蛍光の強度を検出する検出手段と、
前記検出手段により検出された前記光源の点灯及び消灯に対応する蛍光強度に基づいて前記蛍光物質の濃度を推定する演算手段と、
前記演算手段による前記蛍光物質の濃度推定値を表示する表示手段とを備えたことを特徴とする蛍光物質集積性腫瘍の境界識別装置。
A light source that irradiates excitation light of a predetermined wavelength component to a fluorescent substance that has been chemically modified by being accumulated in an affected part of a subject in a living body and intermittently excites the fluorescent substance by repeating lighting and extinguishing thereof,
Light guiding means for guiding the excitation light from the light source to the vicinity of the affected part in the living body,
Detecting means for detecting the intensity of the fluorescence emitted from the fluorescent substance accumulated in the affected part,
Calculation means for estimating the concentration of the fluorescent substance based on the fluorescence intensity corresponding to turning on and off the light source detected by the detection means,
Display means for displaying an estimated value of the concentration of the fluorescent substance by the calculating means.
前記光源は、機械式シャッターと特定の波長近傍成分をもつ光を透過する光学フィルタとを有するハロゲンランプ光源又はメタルハライドランプ光源、又は、前記光源の点灯及び消灯の応答性に優れたLED(発光ダイオード)或はそのLEDに光学フィルタを設けて構成されることを特徴とする請求項1記載の蛍光物質集積性腫瘍の境界識別装置。The light source may be a halogen lamp light source or a metal halide lamp light source having a mechanical shutter and an optical filter that transmits light having a component near a specific wavelength, or an LED (light emitting diode) having excellent responsiveness of turning on and off the light source. 2. The apparatus according to claim 1, wherein the LED is provided with an optical filter. 前記導光手段は、前記蛍光物質が集積する患部に前記励起光を導くと共に、その励起光により当該蛍光物質から放射される蛍光を前記検出手段に導く光ファイバを備えたことを特徴とする請求項1記載の蛍光物質集積性腫瘍の境界識別装置。The light guide unit includes an optical fiber that guides the excitation light to an affected area where the fluorescent substance accumulates, and guides fluorescence emitted from the fluorescent substance by the excitation light to the detection unit. Item 7. The apparatus for identifying a boundary of a fluorescent substance-accumulating tumor according to Item 1. 前記検出手段は、凹型の回折格子、凸型の回折格子、又はレンズを組み合わせてなる回折格子と、光を電気信号に変換する光検出器とから構成されることを特徴とする請求項1記載の蛍光物質集積性腫瘍の境界識別装置。The said detection means is comprised from the diffraction grating which combined the concave-shaped diffraction grating, the convex-shaped diffraction grating, or the lens, and the photodetector which converts light into an electrical signal. Identification device for fluorescent material-accumulating tumor. 前記演算手段は、前記光源の点灯時における前記励起光の強度に対応する第1の波長における測定値をLonとし、前記光源の消灯時における励起光の強度に対応する第1の波長における測定値をLoffとし、前記光源の点灯時に前記検出手段により検出される蛍光の強度に対応する第1の波長と異なる第2の波長における測定値をlonとし、前記光源の消灯時に前記検出手段により検出される蛍光の強度に対応する第1の波長と異なる第2の波長における測定値をloffとし、前記蛍光物質の濃度に対応するパラメータをPとしたときの当該パラメータP=(lon−loff)/(Lon−Loff)、又は、そのパラメータPの変化に対し単調増加又はこのパラメータPと単調減少の関係にある数値を演算するものであることを特徴とする請求項1記載の蛍光物質集積性腫瘍の境界識別装置。The calculation means sets a measurement value at a first wavelength corresponding to the intensity of the excitation light when the light source is turned on to Lon, and a measurement value at a first wavelength corresponding to the intensity of the excitation light when the light source is turned off. Is Loff, a measured value at a second wavelength different from the first wavelength corresponding to the intensity of the fluorescence detected by the detection means when the light source is turned on is lon, and the measurement value is detected by the detection means when the light source is turned off. Where the measured value at the second wavelength different from the first wavelength corresponding to the intensity of the fluorescent light is loff and the parameter corresponding to the concentration of the fluorescent substance is P, the parameter P = (lon-loff) / ( Lon-Loff) or that a numerical value having a monotonic increase or a monotonically decreasing relationship with the parameter P is calculated with respect to a change in the parameter P. Boundary identification apparatus of a fluorescent substance accumulation tumors according to claim 1, symptoms. 前記演算手段により推定される前記患部表面に染料を塗布してマーキングを施すための開口部を有する染料塗布手段と、
前記患部表面の液体を吸引除去する開口部を有する吸引手段とをさらに備え、前記染料塗布手段の開口部及び前記吸引手段の開口部が前記光ファイバの先端部近傍の所定位置に配置されたことを特徴とする請求項3記載の蛍光物質集積性腫瘍の境界識別装置。
A dye application unit having an opening for applying a dye to the affected part surface estimated by the calculation unit and performing marking,
A suction unit having an opening for suctioning and removing the liquid on the surface of the affected part, wherein the opening of the dye application unit and the opening of the suction unit are arranged at predetermined positions near the tip of the optical fiber. The apparatus for identifying a boundary of a fluorescent substance-accumulating tumor according to claim 3, characterized in that:
前記光ファイバの先端部に着脱自在で、且つ、緩やかに湾曲した形状をもつ保護手段をさらに備えたことを特徴とする請求項3記載の蛍光物質集積性腫瘍の境界識別装置。4. The apparatus according to claim 3, further comprising a protection means detachably attached to the tip of the optical fiber and having a gently curved shape. 前記光ファイバの先端部は、ハンドピース型検出器で構成されることを特徴とする請求項3記載の蛍光物質集積性腫瘍の識別装置。4. The apparatus according to claim 3, wherein the distal end of the optical fiber is formed of a handpiece detector.
JP2002256991A 2002-09-02 2002-09-02 Fluorescent substance accumulating tumor boundary identification device Pending JP2004089533A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2002256991A JP2004089533A (en) 2002-09-02 2002-09-02 Fluorescent substance accumulating tumor boundary identification device

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2002256991A JP2004089533A (en) 2002-09-02 2002-09-02 Fluorescent substance accumulating tumor boundary identification device

Publications (1)

Publication Number Publication Date
JP2004089533A true JP2004089533A (en) 2004-03-25

Family

ID=32062045

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2002256991A Pending JP2004089533A (en) 2002-09-02 2002-09-02 Fluorescent substance accumulating tumor boundary identification device

Country Status (1)

Country Link
JP (1) JP2004089533A (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006288457A (en) * 2005-04-06 2006-10-26 Morita Mfg Co Ltd Dental irradiation device
JP2007151873A (en) * 2005-12-06 2007-06-21 Pentax Corp Magnifying endoscope
JP2009542289A (en) * 2006-07-07 2009-12-03 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Optical imaging system and method
JP2010043983A (en) * 2008-08-14 2010-02-25 Sony Corp Optical measuring device
JP2011196867A (en) * 2010-03-19 2011-10-06 Olympus Corp Microscope system, display method of observation image, and program
JP5034953B2 (en) * 2006-01-20 2012-09-26 住友電気工業株式会社 Imaging system
WO2012132790A1 (en) * 2011-03-31 2012-10-04 オリンパス株式会社 Fluorescence observation device
JP2013514156A (en) * 2009-12-15 2013-04-25 エモリー ユニバーシティ System and method for providing real-time anatomical guidance in diagnostic or therapeutic procedures
WO2013115209A1 (en) 2012-01-30 2013-08-08 シーシーエス株式会社 Illumination device for tumor detection and illumination device for examinations
JP2015510418A (en) * 2012-02-13 2015-04-09 コーニンクレッカ フィリップス エヌ ヴェ Photon probe device incorporating a tissue labeling mechanism
US9345389B2 (en) 2010-11-12 2016-05-24 Emory University Additional systems and methods for providing real-time anatomical guidance in a diagnostic or therapeutic procedure
WO2017164101A1 (en) * 2016-03-22 2017-09-28 国立研究開発法人産業技術総合研究所 Light radiation system, control device, light radiation control method, and surgical microscope device
WO2017212617A1 (en) * 2016-06-09 2017-12-14 株式会社島津製作所 Near-infrared imaging apparatus and marker member for near-infrared imaging apparatus
JP2024517549A (en) * 2021-03-12 2024-04-23 ストライカー・ユーロピアン・オペレーションズ・リミテッド Neurosurgical methods and systems for detecting and removing tumor tissue - Patents.com
CN121040833A (en) * 2025-11-03 2025-12-02 中国科学院合肥物质科学研究院 A fluorescence endoscope system and method with real-time adjustable liquid volume and concentration

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006288457A (en) * 2005-04-06 2006-10-26 Morita Mfg Co Ltd Dental irradiation device
JP2007151873A (en) * 2005-12-06 2007-06-21 Pentax Corp Magnifying endoscope
JP5034953B2 (en) * 2006-01-20 2012-09-26 住友電気工業株式会社 Imaging system
JP2009542289A (en) * 2006-07-07 2009-12-03 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Optical imaging system and method
JP2010043983A (en) * 2008-08-14 2010-02-25 Sony Corp Optical measuring device
US9451882B2 (en) 2009-12-15 2016-09-27 Emory University Integrated system and methods for real-time anatomical guidance in a diagnostic or therapeutic procedure
JP2013514156A (en) * 2009-12-15 2013-04-25 エモリー ユニバーシティ System and method for providing real-time anatomical guidance in diagnostic or therapeutic procedures
JP2011196867A (en) * 2010-03-19 2011-10-06 Olympus Corp Microscope system, display method of observation image, and program
US9345389B2 (en) 2010-11-12 2016-05-24 Emory University Additional systems and methods for providing real-time anatomical guidance in a diagnostic or therapeutic procedure
WO2012132790A1 (en) * 2011-03-31 2012-10-04 オリンパス株式会社 Fluorescence observation device
CN103458759A (en) * 2011-03-31 2013-12-18 奥林巴斯株式会社 Fluorescence observation device
US9949645B2 (en) 2011-03-31 2018-04-24 Olympus Corporation Fluorescence imaging apparatus for identifying fluorescence region based on specified processing condition and superimposing fluorescence region at corresponding region in return-light image
JP6006199B2 (en) * 2011-03-31 2016-10-12 オリンパス株式会社 Fluorescence observation equipment
WO2013115209A1 (en) 2012-01-30 2013-08-08 シーシーエス株式会社 Illumination device for tumor detection and illumination device for examinations
JP2015510418A (en) * 2012-02-13 2015-04-09 コーニンクレッカ フィリップス エヌ ヴェ Photon probe device incorporating a tissue labeling mechanism
US10716613B2 (en) 2012-02-13 2020-07-21 Koninklijke Philips N.V. Photonic probe apparatus with integrated tissue marking facility
WO2017164101A1 (en) * 2016-03-22 2017-09-28 国立研究開発法人産業技術総合研究所 Light radiation system, control device, light radiation control method, and surgical microscope device
JPWO2017164101A1 (en) * 2016-03-22 2019-01-24 国立研究開発法人産業技術総合研究所 Light irradiation system, control apparatus, light irradiation control method, and surgical microscope apparatus
WO2017212617A1 (en) * 2016-06-09 2017-12-14 株式会社島津製作所 Near-infrared imaging apparatus and marker member for near-infrared imaging apparatus
CN109310402A (en) * 2016-06-09 2019-02-05 株式会社岛津制作所 Near-infrared imaging device and marking member for near-infrared imaging device
JPWO2017212617A1 (en) * 2016-06-09 2019-04-11 株式会社島津製作所 Near-infrared imaging device and marker member for near-infrared imaging device
JP2024517549A (en) * 2021-03-12 2024-04-23 ストライカー・ユーロピアン・オペレーションズ・リミテッド Neurosurgical methods and systems for detecting and removing tumor tissue - Patents.com
CN121040833A (en) * 2025-11-03 2025-12-02 中国科学院合肥物质科学研究院 A fluorescence endoscope system and method with real-time adjustable liquid volume and concentration

Similar Documents

Publication Publication Date Title
JP7596435B2 (en) Medical imaging devices and methods of use
CN102665559B (en) Excitation, detection, and projection system for visualizing target cancer tissue
JP2023120180A6 (en) Medical imaging devices and methods of use
JP2021100574A6 (en) Medical imaging devices and methods of use
US7764380B2 (en) Hair detection device
EP2105082B1 (en) Fluorescence observing device and fluorescence observing method
EP2061372B1 (en) Apparatus for caries detection
KR101856909B1 (en) Apparatus for Measuring Skin Condition with Multiple Lights
JP2004089533A (en) Fluorescent substance accumulating tumor boundary identification device
JP4954858B2 (en) Fluorescence observation apparatus and endoscope apparatus
EP1167951B1 (en) Fluorescent image obtaining apparatus
US20140085686A1 (en) Fluorescence observation device
US20240138665A1 (en) Dental imaging system and image analysis
JP4316118B2 (en) Fluorescence endoscope device
JP7160898B2 (en) medical observation system
JP2009153621A (en) Biological observation apparatus and endoscope apparatus
JP5080014B2 (en) Imaging system
KR101528610B1 (en) Lighting Device using optical fiber for diagnosing dental caries and fluorosis
US20200305696A1 (en) Tissue detection system and methods for use thereof
JPH07163572A (en) Photochemical diagnostic device
JP2010063839A (en) Endoscopic apparatus
JP2002078670A (en) Fluorescent imaging system
JP2006528045A (en) Fluorescent filter for histological examination and image processing
JP2013244313A (en) Light measuring apparatus
JPWO2013133341A1 (en) Optical measuring device

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20050825

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20080715

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20081111