JP5587955B2 - サンプルの周波数領域画像形成を提供するためのプロセス、構成およびシステム - Google Patents
サンプルの周波数領域画像形成を提供するためのプロセス、構成およびシステム Download PDFInfo
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- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/12—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
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- A61B3/1233—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes using coherent radiation for measuring blood flow, e.g. at the retina
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Description
本出願は、2006年5月10日に出願された米国特許出願第60/799,511号明細書に基づき、それから優先権の利益を主張する。その全開示は、本明細書中に参照として援用される。
本発明に関する調査は、国立衛生研究所−国立癌研究所によって付与された認可番号R33 214033号によって、少なくとも一部分支持されていた。従って、米国政府は本発明において特定の権利を有し得る。
本発明は、光学顕微鏡法を用いて解剖学的構造またはサンプルに関する情報を取得するプロセス、構成およびシステムに関し、より具体的には、解剖学的構造/サンプル(例えば眼の少なくとも一部分)の光周波数領域画像形成を提供するような方法、システムおよび構成に関する。
図1(a)は、本発明に従う直線状の共振器構造において備えられるレーザー光源システム(例えば、1050nmの掃引レーザー光源を含み得る)の例示的な実施形態を示す。この図に示されるように、400mAの注入電流レベルで駆動され得る双方向半導体光増幅器(QPhotonics,Inc.,QSOA−1050)のような利得媒質10が備えられ得る。増幅器の1つのポートは、回折格子30(1200ライン/mm)、100mmおよび50mmの焦点距離をそれぞれ有する2つのレンズ40、42からなるテレスコープ、ならびに多面鏡スキャナー50(例えば、Lincoln Lasers,Inc.,40面)を備え得る波長走査フィルタ20に接続され得る。フィルタの設計バンド幅および自由スペクトル領域は、それぞれ約0.1nmおよび61nmであり得る。増幅器のもう一方のポートは、50/50カプラ60を備え得るループミラーに接続するようにつながれ得る。サグナックループ70もまた、出力カプラとして作動し得る。
図1(b)は、本発明に従う光周波数領域画像形成(OFDI)システムの例示的な実施形態を示す。例えば、光源100として使用され得る掃引レーザーを使用することができる。この例示的なシステムはさらに、光ファイバ干渉計110、ビームスキャナー120、検出器130およびコンピューター140を備える。サンプルアーム150(例えば30%ポート)は、網膜の画像形成のために設計され得る2軸検流計スキャナー装置120に接続され得る。焦点ビームのサイズは組織において約10μm(例えば指標=1.38)であり得る。眼160の入射瞳における屈折力レベルは約550μWであると測定され得、これは、ANSIレーザー安全基準に従うλ=1050nmでの1.9mWの最大暴露レベルをはるかに下回る。参照アーム170(例えば70%ポート)は、透過型可変遅延線180および10%タップカプラ182を利用することができ、データを獲得するためのサンプリングトリガー信号を生成する。
図2(a)は、ピークホールドモード(分解能=0.1nm)において最適なスペクトル分析器を用いて測定された例示的な出力スペクトルを示す。例示的な出力スペクトルは、フィルタの自由スペクトル領域によって測定され、1019〜1081nmで62nmの範囲に及んでいた。このスペクトル範囲は眼の局部の透明領域と一致した。ヒトの硝子体および房水における往復光吸収は、水の公知の吸収特性に基づいて約2dBと5dBとの間であると推定できる(図2(a)に示される)。可変遅延マイケルソン干渉計を用いて、空気中で約4.4mmである、50%の視界を生じる往復遅延として規定されるレーザー出力のコヒーレンス長を測定することは可能である。この値から、0.11nmであるレーザー出力の瞬時のライン幅を測定できる。図2(a)において、ピークホールド出力スペクトル200および光吸収曲線205は、代表的なヒトの硝子体における往復に相当する水中で42mmの伝搬距離を与えられる。
OFDIシステムの例示的な実施形態および例示的な最適化操作パラメーターは、サンプルとして一部の反射体(ニュートラルデンシティフィルタおよび金属鏡)を用いてSNRを最大化するために提供され得る。最大SNRについての例示的な好ましい参照アーム電力は、各検出ポートで2.6μWであり得る。この比較的低い値は、二重平衡検出において完全に抑制されなくてよいレーザーの比較的大きな強度雑音に起因すると考えられ得る。本発明の例示的な実施形態に従う例示的なデータ処理としては、非線形k−空間チューニングを補正するための参照物減算、エンベロープアポダイゼーションまたはウィンドウイング、補間、および分散補正が挙げられ得る。例えば、レーザー光源の不均一スペクトルエンベロープに起因して、干渉信号から参照物を減算することによって画像アーチファクトを除去することができる。適切なウィンドウイング技術を課すことにより干渉縞をアポダイズすることによって、点広がり関数の側帯波を減少させ、画像コントラストを向上させることができる。
本発明に従うシステム、プロセスおよび構成の例示的な実施形態を用いて、例示的なOFDI画像形成を、2人の健康的なボランティア(A:36歳のアジア人男性、B:41歳のカフカス人男性)で行った。焦点サンプルビームが、網膜黄班部を5.2mm(垂直)と6mm(水平)の領域にわたって走査されて、例示的なOFDIシステムは10−20秒にわたって連続的に18,800のAラインを獲得した。図4は、10.6秒で18.8Hzのフレーム率でボランティアAから記録されたサンプルの中心窩および視神経円板の一連の画像250を示す。各画像フレームは、組織内の6.0mm(水平)および1.8mm(深度)にわたる各々のフレーム範囲で47dBを超える反射率範囲まで反転グレースケールテーブル写像を用いて1,000のAライン走査から構築した。例えば、5.2mmの垂直範囲で組織領域を画像化するために200のフレームを10.6秒で獲得した。網膜における解剖学的層は可視化されて、以前に公開されたOCT画像および組織学的所見との相関関係が十分に示された。
眼の後部の3次元トモグラフィーデータを用いて、全深度軸に沿ったピクセル値が、1つの2次元基底部型反射率画像を生成するために統合され得る。図6Aは、従来の全範囲統合法を用いて得た2次元反射率画像(5.3×5.2mm 2 )である前記画像の図4に示される全OFDI画像シーケンスから生成された1つの例示的な統合された反射率画像を示す。前記例示的な画像は、例示的な視神経頭、中心窩、網膜血管および深い脈絡膜血管の外形を示す。しかしながら、深度情報は示されていない。従来の方法によって生成されたこの画像の欠陥を扱うために、本発明のシステム、プロセスおよび構成の例示的な実施形態を用いることによって、選択的領域のみを統合することは可能である。
実験結果は、1050nmで例示的なOFDI技術を用いて生成した画像が、高分解能および高コントラストでヒトの網膜および脈絡膜の広範囲の画像形成を提供することができることを示す。しかしながら、本発明の例示的な実施形態に従うOFDIシステムの例示的な実施形態は、従来の時間領域OCTシステムの使用より一桁高い画像獲得速度を提供することができ、840nmでのSD−OCTシステムと比べて向上したコントラストの脈絡膜画像に役立つ。向上した侵入により、脈絡膜毛細血管および血管ネットワークの深度断面反射率画像を得ることが可能となる。眼低カメラまたは走査レーザー検眼鏡は、従来通り血管系を見るために使用されている。しかしながら、このような方法は、かなり低いレベルの色素形成を有する患者を除いて脈絡膜へと接近するために蛍光またはインドシアニングリーン血管造影を必要とし得る。
図7(a)は、本発明に従う、例えば815−870nmのスペクトル範囲における掃引レーザー光源構成の別の例示的な実施形態を示す。掃引レーザー光源構成部は、自由空間アイソレータ310を有する光ファイバの単方向リング空洞300を備え得る。利得媒質320は、市販の利用可能な半導体光増幅器(例えばSOA−372−850−SM、Superlum Diodes Ltd.)であり得る。備えられ得る腔内スペクトルフィルタ330は、回折格子(例えば830溝/mm)332、4f構造において2つの色消レンズ334、336、および72面多面鏡340(Lincoln lasers,Inc.)を含み得る。多面鏡は1秒につき約600回転で回転し得、43.2kHzの繰り返し率で短波長から長波長まで一方向の掃引を生成することができる。
本発明に従うOFDIシステムの例示的な実施形態は、例示的な波長掃引レーザー構成部を用いて提供することができる。例示的なシステムの構造は、図1(b)に示されるシステムと同様であり得る。レーザー出力は、30/70カプラによって干渉計内の2つの経路に分割され得る。1つの経路(例えば「サンプルアーム」と呼ばれる30%ポート)において、2軸検流計走査(例えばModel、Cambridge Technologies)を介して生物学的サンプルを照射することができる。もう1つの経路「参照アーム」は一般に参照ビームを与える。後方散乱によってサンプルから戻ってくる信号ビームは、参照ビーム(例えば50/50カプラ)と合成され、それによって干渉を生成する。
SdB=S0−10log10(1+a/Pr+Pr/b)−Δ
ここで、S0は散弾雑音限界感受性を示し、Prは参照電力レベルであり、熱雑音および強度雑音において参照電力レベルに相当するaおよびbは、それぞれ、大きさにおいて散弾雑音のレベルと等しくなり、Δは、感受性の損失に寄与する他の要因と関連する調整パラメーターであり得る。増幅自然放出を考慮に入れると、S0は約107dBであり得る。例えば、検出雑音レベル(例えば3.3pA/√Hz)および変換効率(例えば1A/W)からa=17μWである。レーザー(例えば−130dB/Hz)の相対強度雑音および平衡レシーバの抑制効率の18dB共通雑音に基づいて、b=280μWである。例えば、図8(b)の実験データ410に最も適合するのはΔ=8dBを用いて取得され得る。図8(b)は、深度の関数として測定された感受性420のグラフを示す。この例示的な値は、フラット参照スペクトル、サンプル光と参照光との間の偏光ミスマッチ、およびデータ処理におけるアポダイゼーション工程を想定する単純化したモデルに大部分起因し得、各々はいくらかのdBによる感受性の損失に起因するようである。
OFDI画像形成についての例示的な好ましい光源構成は、一般に、均一の出力スペクトルを有する。そのような所望のスペクトルプロファイルを得るために、利得媒質の利得もしくは損失、またはレーザー空洞のフィルタ内部もしくは外部を調節することができる。フィルタは広帯域可変減衰器であり得、その送信はレーザーチューニングと同調して制御され得る。例示的なフィルタは、所望の透過スペクトルを有する受動的スペクトルフィルタであり得る。利得媒質は好ましくは半導体光増幅器であり得、その利得は注入電流をフィルタチューニングと同調して増幅器に調節することによって変化され得る。図10(a)および10(b)は、それぞれ、本発明に従う調節方法の例示的な実施形態を使用する例示的な出力チューニングトレース480、使用ない例示的な出力チューニングトレース490のグラフを示す。この例示的な方法はまた、半導体利得チップの所定の光損傷閾値についての出力電力およびチューニング範囲を最大化または少なくとも増加させるために効果的であり得る。
眼の網膜および脈絡膜において血流を検出および定量化する能力は、加齢性黄班変性の診断のようないくらかの臨床応用において効果を有し得る。OFDI信号の位相から流量情報を抽出するいくらかの方法は、当該分野において公知である。しかしながら、これらの例示的な従来の方法は、サンプリングの間にわたって、2つの連続的なAライン走査の間に有意なビームのオーバーラップを必要とし、それによって、位相確度と画像獲得速度との間に望んでいない障害を引き起こす。本発明に従うシステム、プロセスおよび構成の例示的な実施形態を用いて2つのAライン走査の位相値を比較する代わりに、単一のAライン内の異なる時点または波長に対応する複数の位相値を抽出し、その値と参照位相値とを比較することができる。この例示的な手段は、単一のAライン走査の間の多数の時点での流速の測定を提供し、より速いビーム走査および画像獲得速度を可能にする。そのような手段は、多くの用途において受け入れられるような低下した位相または速度測定精度において使用され得る。
Claims (14)
- サンプルの少なくとも1つの部分の1つの3次元画像のための第1のデータを受信するように構成された少なくとも1つの構成部を備える装置であって、
前記第1のデータは、前記サンプルおよび参照物から得られた信号から生成された光干渉信号と関連付けられ、
前記少なくとも1つの構成部は、前記サンプルの少なくとも1つの部分と関連付けられた1つの2次元画像を生成するために前記第1のデータの全ての部分より少ない領域を第2のデータに変換するように構成され、
前記少なくとも1つの構成部は、さらに、前記サンプルの少なくとも1つの特性に基づいて前記領域を自動的に選択するように構成され、
前記全ての部分は、前記サンプル内の内部構造と関連付けられる、装置。 - 前記サンプルは解剖学的構造である、請求項1に記載の装置。
- 前記領域は、網膜または脈絡膜のうちの少なくとも1つの少なくとも1つの部分である、請求項1に記載の装置。
- 前記2次元画像は、前記領域の統合された反射率プロファイルと関連付けられる、請求項1に記載の装置。
- 前記2次元画像は、血液またはリンパ管ネットワークのうちの少なくとも1つと関連付けられる、請求項4に記載の装置。
- 前記少なくとも1つの構成部は、前記領域内の反射率に基づいて、前記領域の少なくとも1つの部位の少なくとも1つの位置を決定することによって前記領域を自動的に選択する、請求項1に記載の装置。
- サンプルの少なくとも1つの部分の1つの3次元画像のための第1のデータを受信する工程であって、前記第1のデータは、前記サンプルおよび参照物から得られた信号から生成された光干渉信号と関連付けられる工程と、
前記サンプルの少なくとも1つの部分と関連付けられた1つの2次元画像を生成するために前記第1のデータの全ての部分より少ない領域を第2のデータに変換する工程と、
前記サンプルの少なくとも1つの特性に基づいて、前記領域を自動的に選択する工程と、を包含するプロセスであって、前記全ての部分は、前記サンプル内の内部構造と関連付けられる、処理方法。 - 処理装置によって実行されるプログラムであって、前記処理装置は、
サンプルの少なくとも1つの部分の1つの3次元画像のための第1のデータを受信する、第1の命令セットであって、前記第1のデータは、前記サンプルおよび参照物から得られた信号から生成された光干渉信号と関連付けられる、第1の命令セットと、
前記サンプルの少なくとも1つの部分と関連付けられた1つの2次元画像を生成するために、前記第1のデータの全ての部分より少ない領域を第2のデータに変換する、第2の命令セットと、
前記サンプルの少なくとも1つの特性に基づいて、前記領域を自動的に選択する、第3の命令セットと、を含む、プログラムであって、前記全ての部分は、前記サンプル内の内部構造と関連付けられる、プログラム。 - 前記少なくとも1つの構成部によって受信された前記第1のデータは、3次元トモグラフィーデータである、請求項1に記載の装置。
- 前記少なくとも1つの特性は、反射率プロファイルである、請求項1に記載の装置。
- 前記第1のデータは、3次元トモグラフィーデータである、請求項7に記載の方法。
- 前記少なくとも1つの特性は、反射率プロファイルである、請求項7に記載の方法。
- 前記第1のデータは、3次元トモグラフィーデータである、請求項8に記載のプログラム。
- 前記少なくとも1つの特性は、反射率プロファイルである、請求項8に記載のプログラム。
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WO2007133961A2 (en) | 2007-11-22 |
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US10413175B2 (en) | 2019-09-17 |
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EP2517616A3 (en) | 2013-03-06 |
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