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- JP2014025899A5 JP2014025899A5 JP2012168841A JP2012168841A JP2014025899A5 JP 2014025899 A5 JP2014025899 A5 JP 2014025899A5 JP 2012168841 A JP2012168841 A JP 2012168841A JP 2012168841 A JP2012168841 A JP 2012168841A JP 2014025899 A5 JP2014025899 A5 JP 2014025899A5
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- 230000003287 optical Effects 0.000 claims description 53
- 210000001519 tissues Anatomy 0.000 claims description 49
- 239000000126 substance Substances 0.000 claims description 48
- 238000005259 measurement Methods 0.000 claims description 37
- 230000031700 light absorption Effects 0.000 claims description 17
- 230000001747 exhibiting Effects 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 2
- 235000013405 beer Nutrition 0.000 claims 1
- 238000010226 confocal imaging Methods 0.000 description 7
- 102000001554 Hemoglobins Human genes 0.000 description 6
- 108010054147 Hemoglobins Proteins 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000001124 Body Fluids Anatomy 0.000 description 1
- 210000003491 Skin Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002238 attenuated Effects 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
Description
また、前記の特許文献４に記載の酸素飽和度測定方法と装置は、測定対象が酸素化ヘモグロビンと還元ヘモグロビンの２種類であるときに適用することができるが、生体組織内部の体液成分や水分のように１種類に限られる場合には測定精度が大きく低下するという問題がある。これは、皮下の特定の深さの位置にある正規焦点面と非正規焦点面の領域で、入射光が減衰する要素、例えば両者の面の間で発生する「光反射」による光減衰と「光吸収」による光減衰を区別できないためである。前記の特許文献４に記載されているように酸素飽和度の算出であれば、酸素化ヘモグロビンと還元ヘモグロビンの両方で「光反射」による光減衰が発生するため、酸素化ヘモグロビンと還元ヘモグロビンの比を算出する際に、この問題は相殺されるか、若しくは両者の面の反射による入射光強度の比が既知であるため考慮しなくてもよくなる。しかし、体液成分量や水分量の測定は、1種類の測定対象の量から算出する必要があるため、「光反射」による光減衰が相殺できず、「光反射」と「光吸収」による光減衰が区別できないという問題を解決する方法が必要となる。さらに、前記の特許文献４に記載の「反射光がどの深さ位置から反射しているかを把握する技術」は、フーリエ解析による複雑な計測手段と計算手順が必要になる。
In addition, the oxygen saturation measuring method and apparatus described in Patent Document 4 can be applied when the measurement target is two types of oxygenated hemoglobin and reduced hemoglobin. Thus, there is a problem in that the measurement accuracy is greatly reduced when the number is limited to one. This is a region of normal focal plane and non-normal focal plane at a specific depth position under the skin, in which incident light is attenuated, for example, light attenuation caused by “light reflection” generated between both planes and “ This is because light attenuation due to “light absorption” cannot be distinguished. If the oxygen saturation is calculated as described in Patent Document 4, light attenuation due to “light reflection” occurs in both oxygenated hemoglobin and reduced hemoglobin, so the ratio of oxygenated hemoglobin to reduced hemoglobin. This problem can be offset when calculating, or the ratio of the incident light intensity due to reflection of both surfaces is known and need not be considered. However, since the measurement of the amount of body fluid and the amount of water needs to be calculated from the amount of one type of measurement object, the light attenuation due to “light reflection” cannot be offset, and the light due to “light reflection” and “light absorption” What is needed is a way to solve the problem that attenuation is indistinguishable. Furthermore, the “technology for grasping from which depth position the reflected light is reflected” described in Patent Document 4 requires complicated measuring means and calculation procedures by Fourier analysis.
すなわち、本発明の構成は以下の通りである。
［１］本発明は、生体組織内に存在し、近赤外域に特異的な光吸収を有する物質の含有量の測定方法であって、次の（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）、すなわち（Ａ）前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１を測定用波長とし、前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２を補正用波長として選び、生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の波長λ１及び波長λ２において前記の正規焦点面及び非正規焦点面の反射光強度を共焦点光学系で測定する手段、（Ｂ）前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって補正係数を算出する手段、（Ｃ）前記の測定用波長λ１における入射光の減衰要素である光反射と光吸収のうち、光反射の要素を相殺するために、前記の補正係数を前記の測定用波長λ１における非正規焦点面の反射光強度に乗算して補正済非正規反射光強度を算出する手段、及び（Ｄ）前記の補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する前記物質の含有量を求める手段、を有することを特徴とする生体組織内に存在する物質量の測定方法を提供する。
［２］本発明は、前記の（Ａ）の手段において、前記の波長λ１及び波長λ２における反射光強度の測定が、前記の正規焦点面からの反射光及び非正規焦点面からの反射光をそれぞれ別の共焦点光学系で同時に検出することによって行われることを特徴とする前記［１］に記載の生体組織内に存在する物質量の測定方法を提供する。
［３］本発明は、前記の（Ａ）の手段において、前記の波長λ１及び波長λ２の反射光強度の測定が、前記の正規焦点面からの反射光及び非正規焦点面からの反射光を、焦点位置の切り替えが可能な共焦点光学系で時系列的に検出することによって行われることを特徴とする前記［１］に記載の生体組織内に存在する物質量の測定方法を提供する。
［４］本発明は、前記の（Ａ）〜（Ｄ）の手段を、前記生体組織内の深さ方向に設ける２箇所以上の深さ位置で繰り返して、前記生体組織における深度と前記生体組織内に存在する前記物質の含有量との関係を把握することによって、測定対象生体組織と測定対象外生体組織の前記物質の含有量を可視化して区別することを特徴とする前記［１］〜［３］の何れかに記載の生体組織内に存在する物質量の測定方法を提供する。
また、本発明は、前記の波長λ１が、前記の特異的な光吸収を示す吸光度スペクトルにおいて吸収ピーク値の１／２以上の吸光度を示す波長領域内に含まれる少なくとも１つの波長であり、前記の波長λ２が、前記の吸光度スペクトルにおいて吸収ピーク値の１／２未満の吸光度を示し、前記の波長領域内に含まれない波長の少なくとも１つの波長であることを特徴とする前記［１］〜［４］に記載の生体組織内に存在する物質量の測定方法であってもよい。
［５］本発明は、前記の生体組織内に存在する物質量が、水分量であることを特徴とする前記［１］〜［４］の何れかに記載の生体組織内に存在する物質量の測定方法を提供する。
［６］本発明は、生体組織内に存在し、近赤外域に特異的な光吸収を有する物質の含有量の測定装置であって、少なくとも、前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１で発光する近赤外線光源及び前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２において発光する近赤外線光源と、無限系対物レンズ若しくは有限系対物レンズと、入射光又は反射光を分けるためのビームスプリッターと、生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の正規焦点面及び非正規焦点面からの反射光強度をそれぞれ別の共焦点光学系によって収束させる手段と、波長λ１の近赤外線強度を識別できる近赤外線検出器及び波長λ２の近赤外線強度を識別できる近赤外線検出器と、前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって算出される補正係数を前記の測定用波長λ１における非正規焦点面の反射光強度に乗算することによって得られる補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する物質の含有量を計算するための演算処理手段と、を有することを特徴とする生体組織内に存在する物質量の測定装置を提供する。
また、本発明は、前記［６］に記載の測定装置において、前記の波長λ１又は波長λ２の近赤外光がそれぞれ生体組織内に存在する物質に照射されるときに前記の正規焦点面又は非正規焦点面から発する反射光は、前記の無限系の対物レンズを通り、次いで前記のビームスプリッターの通過によって少なくとも２個以上に分けられ、前記２個以上に分けられた反射光のうち、前記の正規焦点面からの反射光は、前記のビームスプリッターから距離ａだけ離れた共焦点光学系ユニットの共焦点用結像レンズを通った後、前記の共焦点結像レンズから距離ｂだけ離れた共焦点用ピンホールを通過して、近赤外線検出器で検出できるように構成され、さらに前記のビームスプリッターの通過後の反射光のうち、前記の非正規焦点面からの反射光は、前記のビームスプリッターから距離ｃだけ離れた前記の共焦点光学系ユニットとは別の共焦点光学系ユニットの共焦点用結像レンズを通り、該共焦点結像レンズから距離ｄだけ離れた前記の共焦点用ピンホールとは別の共焦点用ピンホールを通過して、前記の近赤外線検出器とは別の近赤外線検出器で検出できるように構成されており、前記のａとｃとの距離及び前記のｂとｄとの距離を対比するとき、ａ＝ｃ及びｂ≠ｄ、ａ≠ｃ及びｂ＝ｄ、若しくはａ≠ｃ及びｂ≠ｄとなるように、前記の異なる共焦点光学系ユニットのそれぞれが配置されることを特徴とする生体組織内に存在する物質量の測定装置であってもよい。
また、本発明は、前記［６］に記載の測定装置において、前記の波長λ１又は波長λ２の近赤外光がそれぞれ生体組織内に存在する物質に照射されるときに前記の正規焦点面又は非正規焦点面から発する反射光は、前記の有限系の対物レンズを通り、次いで前記のビームスプリッターの通過によって少なくとも２個以上に分けられ、前記２個以上に分けられた反射光のうち、前記の正規焦点面からの反射光は、前記のビームスプリッターから距離ｅだけ離れた共焦点光学系ユニットの共焦点用ピンホールを通った後、近赤外線検出器で検出できるように構成され、さらに前記のビームスプリッターの通過後の反射光のうち、前記の非正規焦点面からの反射光は、前記のビームスプリッターから距離ｆだけ離れた前記の共焦点光学系ユニットとは別の共焦点光学系ユニットの共焦点用結像ピンホールを通った後、前記の近赤外線検出器とは別の近赤外線検出器で検出できるように構成されており、前記のｅとｆとの距離を対比するとき、ｅ≠ｆとなるように、前記の異なる共焦点光学系ユニットのそれぞれが配置されることを特徴とする生体組織内に存在する物質量の測定装置であってもよい。
［７］本発明は、前記［６］に記載の測定装置が、前記の正規焦点面及び非正規焦点面の深さ位置の調整を容易にするために、前記のビームスプリッターの通過によって少なくとも２個以上に分かれた反射光のうち、集光する光を並行光にする凹レンズを、少なくとも1つの光路の光軸上に搭載することによって、前記の２個以上のそれぞれの光路の光軸上に配置されるレンズの屈折率の合計が前記のそれぞれの光路で異なるように構成されることを特徴とする生体組織内に存在する物質量の測定装置を提供する。
［８］本発明は、生体組織内に存在し、近赤外域に特異的な光吸収を有する物質の含有量の測定装置であって、少なくとも、前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１で発光する近赤外線光源及び前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２で発光する近赤外線光源と、無限系対物レンズ若しくは有限系対物レンズと、入射光又は反射光を分けるためのビームスプリッターと、生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の正規焦点面及び非正規焦点面からの反射光強度を、光軸方向に移動可能な結像レンズとピンホールとを有する共焦点光学系、及び前記の無限系対物レンズ若しくは有限系対物レンズと前記の共焦点光学系との間に配置する光軸方向に移動可能なレンズ又は交換可能な焦点距離の異なるレンズ群から構成される焦点位置の切り替えが可能な光学系によって収束させる手段と、波長λ１の近赤外線強度を識別できる近赤外線検出器及び波長λ２の近赤外線強度を識別できる近赤外線検出器と、前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって算出される補正係数を、前記の測定用波長λ１における非正規焦点面の反射光強度に乗算することによって得られる補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する物質の含有量を計算するための演算処理手段と、を有することを特徴とする生体組織内に存在する物質量の測定装置を提供する。
また、本発明は、前記の共焦点光学系ユニットの共焦点用結像レンズ、共焦点用ピンホール、近赤外線光検出器、及び凹レンズの少なくとも1つ以上の部品が光軸方向に移動可能な部品を有することを特徴とする前記［６］〜［８］の何れかに記載の生体組織内に存在する物質量の測定装置であってもよい。
また、本発明は、前記［６］〜［８］に記載の測定装置が、さらに、前記測定装置を支持固定し、前記測定装置と前記生体組織の表面との距離を、前記生体組織内の深さ方向に設ける２箇所以上の深さ位置に応じて所要の長さに調整することによって測定深度を変えることができる手段を有することを特徴とする生体組織内に存在する物質量の測定装置であってもよい。
また、本発明は、前記の前記の生体組織内に存在する物質の含有量が、水分量であることを特徴とする前記［６］〜［８］に記載の生体組織内に存在する物質量の測定装置であってもよい。
That is, the configuration of the present invention is as follows.
[1] The present invention is a method for measuring the content of a substance that exists in a living tissue and has specific light absorption in the near infrared region, and includes the following (A), (B), (C) and (D), that is, (A) at least one wavelength λ1 of the wavelength exhibiting the specific light absorption is used as a measurement wavelength, and at least one wavelength λ2 of a wavelength that is not easily absorbed by the substance is used as a correction wavelength. When the measurement positions having different depths from the surface of the living tissue are the normal focal plane and the non-normal focal plane, the reflected light intensities of the normal focal plane and the non-normal focal plane at the wavelength λ1 and the wavelength λ2 are obtained. Means for measuring with a confocal optical system; (B) the intensity ratio between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2 (normal reflected light intensity / non-normal reflected light intensity); ) Means for calculating a correction coefficient by (C) Of the light reflection and light absorption, which are attenuation factors of incident light at the regular wavelength λ1, in order to cancel out the light reflection component, the correction coefficient is used as the reflected light intensity of the non-regular focal plane at the measurement wavelength λ1. And (D) the corrected non-regular reflected light intensity and the reflected light intensity of the normal focal plane measured at the measurement wavelength λ1. And means for determining the content of the substance existing in a region sandwiched between the normal focal plane and the non-normal focal plane in accordance with Lambert-Beer's law. A method for measuring the amount of a substance to be produced is provided.
[2] According to the present invention, in the means of (A), the reflected light intensity at the wavelength λ1 and the wavelength λ2 is measured by reflecting the reflected light from the normal focal plane and the reflected light from the non-normal focal plane. The method for measuring the amount of a substance present in a living tissue according to the above [1], wherein the method is performed by simultaneously detecting with different confocal optical systems.
[3] According to the present invention, in the means (A), the reflected light intensity of the wavelength λ1 and the wavelength λ2 is measured by reflecting the reflected light from the normal focal plane and the reflected light from the non-normal focal plane. The method for measuring the amount of a substance present in a living tissue according to the above [1] is provided by performing time series detection with a confocal optical system capable of switching a focal position.
[4] In the present invention, the above-mentioned means (A) to (D) are repeated at two or more depth positions provided in the depth direction in the living tissue, and the depth in the living tissue and the living tissue [1] to [1], wherein the content of the substance in the measurement target biological tissue and the measurement target biological tissue is visualized and distinguished by grasping the relationship with the content of the substance present in the body. [3] A method for measuring the amount of a substance present in a living tissue according to any one of [3] is provided.
In the present invention, the wavelength λ1 is at least one wavelength included in a wavelength region showing an absorbance of 1/2 or more of an absorption peak value in the absorbance spectrum showing the specific light absorption, The wavelength [lambda] 2 of [1] to [1] is characterized in that in the absorbance spectrum, the absorbance λ2 is less than ½ of the absorption peak value and is at least one wavelength not included in the wavelength region. [4] The method for measuring the amount of a substance present in a living tissue may be used .
[ 5 ] In the present invention, the amount of the substance present in the living tissue according to any one of [1] to [ 4 ], wherein the amount of the substance present in the living tissue is a moisture content. Provides a measurement method.
[ 6 ] The present invention is an apparatus for measuring the content of a substance that is present in a living tissue and has specific light absorption in the near infrared region, and includes at least a wavelength that exhibits the specific light absorption. A near-infrared light source that emits light at one wavelength λ1, a near-infrared light source that emits light at at least one wavelength λ2, which is not easily absorbed by the substance, an infinite objective lens or a finite objective lens, and incident light or reflected light And the beam splitter for separating the normal and the normal focal plane and the non-normal focal plane at different measurement positions from the surface of the living tissue, the reflected light intensity from the normal focal plane and the non-normal focal plane is respectively Means for focusing by another confocal optical system, a near-infrared detector capable of identifying near-infrared intensity of wavelength λ1, a near-infrared detector capable of identifying near-infrared intensity of wavelength λ2, and The correction wavelength calculated by the intensity ratio between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2 (normal reflected light intensity / non-normal reflected light intensity) is the measurement wavelength. Using the corrected non-regular reflected light intensity obtained by multiplying the reflected light intensity of the non-normal focal plane at λ 1 and the reflected light intensity of the normal focal plane measured at the measurement wavelength λ 1, Lambert Bale's according to the law, present in the living tissue, characterized in that it comprises a and a processing means for calculating the amount of material present in a region interposed between said normal focal plane non-normal focal plane Provided is an apparatus for measuring the amount of substance to be used.
Further, the present invention provides the measurement apparatus according to [ 6 ], wherein the normal focal plane or the near-infrared light having the wavelength λ1 or λ2 is irradiated to a substance existing in a living tissue, respectively. The reflected light emitted from the non-regular focal plane passes through the infinite objective lens and is then divided into at least two by passing through the beam splitter , and the reflected light divided into the two or more The reflected light from the normal focal plane passes through the confocal imaging lens of the confocal optical system unit separated by a distance a from the beam splitter and then separated from the confocal imaging lens by a distance b. passes through the confocal pinhole, is configured to be detected by a near-infrared detector, further out of the beam splitter after passing through the reflected light, the reflected light from the non-regular focal plane of said, Serial through the confocal imaging lens of different confocal optical system unit and the confocal optical unit at a distance c from the beam splitter, from the confocal imaging lens distance d apart in the It is configured to pass through a confocal pinhole different from the confocal pinhole and be detected by a near-infrared detector different from the near-infrared detector. When comparing the distance and the distance between b and d, the different confocal optics are set such that a = c and b ≠ d, a ≠ c and b = d, or a ≠ c and b ≠ d. Each of the system units may be arranged and may be a measuring device for the amount of substance existing in the living tissue.
Further, the present invention provides the measurement apparatus according to [ 6 ], wherein the normal focal plane or the near-infrared light having the wavelength λ1 or λ2 is irradiated to a substance existing in a living tissue, respectively. Reflected light emitted from the non-regular focal plane passes through the finite system objective lens, and then is divided into at least two by passing through the beam splitter. Of the reflected light divided into the two or more, The reflected light from the normal focal plane is passed through the confocal pinhole of the confocal optical system unit separated by a distance e from the beam splitter, and is then configured to be detected by a near-infrared detector. of the reflected light after passing through the beam splitter, the reflected light from the non-regular focal plane of said, said confocal optical unit at a distance f from the beam splitter After passing through the confocal imaging pinhole of another confocal optical system unit, it is configured so that it can be detected by a near-infrared detector different from the near-infrared detector. Each of the different confocal optical system units may be arranged so that e ≠ f when comparing the distances of the distances, and the apparatus may measure the amount of a substance present in the living tissue. .
[ 7 ] The present invention provides the measurement apparatus according to [ 6 ], wherein the measurement apparatus according to [ 6 ] is configured to pass at least 2 through the beam splitter in order to facilitate the adjustment of the depth positions of the normal focal plane and the non-normal focal plane. Among the reflected light divided into more than one, a concave lens that converts the collected light into parallel light is mounted on the optical axis of at least one optical path, so that the optical axis of each of the two or more optical paths is Provided is a device for measuring the amount of a substance present in a living tissue, characterized in that the total refractive index of lenses arranged is different in each of the optical paths.
[8] The present invention is an apparatus for measuring the content of a substance that is present in a living tissue and has specific light absorption in the near infrared region, and includes at least a wavelength that exhibits the specific light absorption. A near-infrared light source that emits light at one wavelength λ1, a near-infrared light source that emits light at at least one wavelength λ2, which is difficult to absorb light by the substance, an infinite objective lens or a finite objective lens, and incident light or reflected light When the beam splitter and the measurement position having a different depth from the surface of the biological tissue are the normal focal plane and the non-normal focal plane, the reflected light intensity from the normal focal plane and the non-normal focal plane, A confocal optical system having an imaging lens movable in the optical axis direction and a pinhole, and in the optical axis direction arranged between the infinite objective lens or the finite objective lens and the confocal optical system A means for focusing by a movable lens or an optical system capable of switching a focal position composed of interchangeable lens groups having different focal lengths, a near-infrared detector capable of identifying near-infrared intensity of wavelength λ1, and wavelength λ2 A near-infrared detector that can identify the near-infrared intensity, and an intensity ratio between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2 (normal reflected light intensity / non-normal reflected light intensity) ) And the corrected non-regular reflected light intensity obtained by multiplying the reflected light intensity of the non-normal focal plane at the measurement wavelength λ1 and the normal measured at the measurement wavelength λ1. Using the reflected light intensity of the focal plane, the content of the substance present in the region sandwiched between the normal focal plane and the non-normal focal plane is measured according to the Lambert-Beer law. Providing a processing means for calculation, the measuring apparatus of substance amount present in the body tissue, characterized in that it comprises a.
In the present invention, at least one component of the confocal imaging lens, the confocal pinhole, the near-infrared light detector, and the concave lens of the confocal optical system unit is movable in the optical axis direction. The apparatus for measuring an amount of a substance present in a living tissue according to any one of the above [ 6 ] to [ 8 ], which includes a part.
In the present invention, the measurement device according to any one of [ 6 ] to [ 8 ] further supports and fixes the measurement device, and determines the distance between the measurement device and the surface of the biological tissue within the biological tissue. A device for measuring the amount of a substance present in a living tissue, characterized by having means capable of changing the measurement depth by adjusting to a required length according to two or more depth positions provided in the depth direction It may be .
In the present invention, the amount of the substance present in the living tissue according to any one of [6] to [8] , wherein the content of the substance present in the living tissue is a water content. The measuring device may be used .
第１の特徴は、共焦点光学系の対物レンズと共焦点ユニットの間にハーフミラー等のビームスプリッターを設置して光路を２個に分け、２個の光路上両方に光検出器を設置し、２個の光路それぞれに対してハーフミラー等のビームスプリッターと光検出器との間に、共焦点ユニットの共焦点用結像レンズと共焦点用ピンホールを設置し、少なくとも片方の光路に並行光でない光を平行にする凹レンズの機能を有する光学レンズを設置し、それぞれの光路で１個の焦点面だけからの反射光が共焦点用ピンホールを通過できる機能を有し、異なる深さにある２個の焦点面を正規焦点面と非正規焦点面として、正規焦点面だけからの反射光を正規反射光として、非正規焦点面からの反射光を非正規反射光として、正規反射光と非正規反射光をそれぞれの光検出器から同時に取得する機能を有する装置である。
The first feature is that a beam splitter such as a half mirror is installed between the objective lens of the confocal optical system and the confocal unit to divide the optical path into two, and a photodetector is installed on both of the two optical paths. , between the two optical path beam splitter and the photodetector, such as a half mirror for each established a confocal imaging lens and the confocal pinhole for confocal unit at least one of parallel to the optical path An optical lens having the function of a concave lens that collimates light that is not light is installed, and the reflected light from only one focal plane can pass through the confocal pinhole in each optical path, at different depths. Two focal planes are designated as a regular focal plane and a non-regular focal plane, reflected light from only the regular focal plane as regular reflected light, reflected light from the non-regular focal plane as non-regular reflected light, Non-regular reflected light It is a device having a function of simultaneously acquired from the photodetector.
本発明で使用する無限系の対物レンズを使用した共焦点光学系に対して、対物レンズと共焦点ユニットの間にハーフミラー等のビームスプリッターを設置して光路が２個に分けられる。ここで、共焦点ユニットとは、共焦点用のピンホールと、光を集光する機能を有する光学レンズを有するものとする。このとき、ハーフミラー等のビームスプリッターを設置する位置は、出来るだけ対物レンズに近いことが望ましい。ハーフミラーは２個の光路の光強度が等しい強度で分けられるため望ましい。ハーフミラーの角度は、光路に対して４５度の角度で設置し、２個の光路の角度が９０度になることが望ましい。ただし、ここで光路を分ける数は２個と記載したが、これは説明を簡潔にするためのものであって、光路を２個以上に分けた装置として設計することも可能である。また、入射光源の光路は、内容を分かりやすくするため省略する。 In contrast to the confocal optical system using the infinite objective lens used in the present invention, a beam splitter such as a half mirror is installed between the objective lens and the confocal unit, and the optical path is divided into two. Here, the confocal unit includes a confocal pinhole and an optical lens having a function of collecting light. At this time, the position where the beam splitter such as a half mirror is installed is preferably as close to the objective lens as possible. Half mirror desirable because the light intensity of the two optical paths are separated by equal intensity. The angle of the half mirror is preferably set at an angle of 45 degrees with respect to the optical path, and the angle of the two optical paths is preferably 90 degrees. However, although the number of dividing the optical path is described as two here, this is for simplifying the explanation, and it is also possible to design the apparatus as having two or more optical paths. Further, the optical path of the incident light source is omitted for easy understanding of the contents.
Claims (8)
（Ａ）前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１を測定用波長とし、前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２を補正用波長として選び、生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の波長λ１及び波長λ２において前記の正規焦点面及び非正規焦点面の反射光強度を共焦点光学系で測定する手段、
（Ｂ）前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって補正係数を算出する手段、
（Ｃ）前記の測定用波長λ１における入射光の減衰要素である光反射と光吸収のうち、光反射の要素を相殺するために、前記の補正係数を前記の測定用波長λ１における非正規焦点面の反射光強度に乗算して補正済非正規反射光強度を算出する手段、及び
（Ｄ）前記の補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する前記物質の含有量を求める手段、
を有することを特徴とする生体組織内に存在する物質量の測定方法。 A method for measuring the content of a substance that exists in a living tissue and has specific light absorption in the near-infrared region, and includes the following (A), (B), (C), and (D), that is, (A ) At least one wavelength λ1 of the wavelength exhibiting specific light absorption is used as a measurement wavelength, and at least one wavelength λ2 of light that is difficult to be absorbed by the substance is selected as a correction wavelength. When the measurement positions having different depths are the normal focal plane and the non-normal focal plane, the reflected light intensities of the normal focal plane and the non-normal focal plane are measured by the confocal optical system at the wavelength λ1 and the wavelength λ2. means,
(B) Means for calculating a correction coefficient based on an intensity ratio (normal reflected light intensity / non-normal reflected light intensity) between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2.
(C) In order to cancel out the light reflection component of light reflection and light absorption, which are attenuation factors of incident light at the measurement wavelength λ1, the correction factor is used as a non-normal focus at the measurement wavelength λ1. Means for calculating the corrected non-normal reflected light intensity by multiplying the reflected light intensity of the surface, and (D) reflection of the normal focal plane measured at the corrected non-normal reflected light intensity and the measurement wavelength λ1. Means for determining the content of the substance present in a region sandwiched between the normal focal plane and the non-normal focal plane according to Lambert-Beer law using light intensity;
A method for measuring the amount of a substance present in a living tissue, comprising:
前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１で発光する近赤外線光源及び前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２において発光する近赤外線光源と、
無限系対物レンズ若しくは有限系対物レンズと、
入射光又は反射光を分けるためのビームスプリッターと、
生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の正規焦点面及び非正規焦点面からの反射光強度をそれぞれ別の共焦点光学系によって収束させる手段と、
波長λ１の近赤外線強度を識別できる近赤外線検出器及び波長λ２の近赤外線強度を識別できる近赤外線検出器と、
前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって算出される補正係数を前記の測定用波長λ１における非正規焦点面の反射光強度に乗算することによって得られる補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する物質の含有量を計算するための演算処理手段と、
を有することを特徴とする生体組織内に存在する物質量の測定装置。 A device for measuring the content of a substance present in a living tissue and having specific light absorption in the near infrared region,
A near-infrared light source that emits light at at least one wavelength λ1 of the wavelength exhibiting specific light absorption, and a near-infrared light source that emits light at at least one wavelength λ2 that is difficult to be absorbed by the substance,
An infinite objective lens or a finite objective lens,
A beam splitter for separating incident light or reflected light;
When the measurement positions with different depths from the surface of the biological tissue are the normal focal plane and non-normal focal plane, the reflected light intensity from the normal focal plane and non-normal focal plane is converged by separate confocal optical systems. Means to
A near-infrared detector capable of identifying near-infrared intensity of wavelength λ1, and a near-infrared detector capable of identifying near-infrared intensity of wavelength λ2,
The correction coefficient calculated by the intensity ratio (normal reflected light intensity / non-normal reflected light intensity) between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2 is used for the measurement. Using the corrected non-regular reflected light intensity obtained by multiplying the reflected light intensity of the non-normal focal plane at the wavelength λ1 and the reflected light intensity of the normal focal plane measured at the measurement wavelength λ1, Lambert Bale In accordance with the above law, arithmetic processing means for calculating the content of the substance present in the region sandwiched between the normal focal plane and the non-normal focal plane ,
An apparatus for measuring the amount of a substance present in a living tissue, comprising:
前記の特異的な光吸収を示す波長の少なくとも１つの波長λ１で発光する近赤外線光源及び前記の物質に光吸収されにくい波長の少なくとも１つの波長λ２で発光する近赤外線光源と、
無限系対物レンズ若しくは有限系対物レンズと、
入射光又は反射光を分けるためのビームスプリッターと、
生体組織の表面から深さの異なる測定位置を正規焦点面及び非正規焦点面としたときに、前記の正規焦点面及び非正規焦点面からの反射光強度を、光軸方向に移動可能な結像レンズとピンホールとを有する共焦点光学系、及び前記の無限系対物レンズ若しくは有限系対物レンズと前記の共焦点光学系との間に配置する光軸方向に移動可能なレンズ又は交換可能な焦点距離の異なるレンズ群から構成される焦点位置の切り替えが可能な光学系によって収束させる手段と、
波長λ１の近赤外線強度を識別できる近赤外線検出器及び波長λ２の近赤外線強度を識別できる近赤外線検出器と、
前記の補正用波長λ２における正規焦点面の反射光強度と非正規焦点面の反射光強度との強度比（正規反射光強度／非正規反射光強度）によって算出される補正係数を、前記の測定用波長λ１における非正規焦点面の反射光強度に乗算することによって得られる補正済非正規反射光強度及び前記の測定用波長λ１において測定される正規焦点面の反射光強度を用いて、ランベルト・ベールの法則に従って、前記の正規焦点面と非正規焦点面との間に挟まれた領域に存在する物質の含有量を計算するための演算処理手段と、
を有することを特徴とする生体組織内に存在する物質量の測定装置。 A device for measuring the content of a substance present in a living tissue and having specific light absorption in the near infrared region,
A near-infrared light source that emits light at at least one wavelength λ1 of the wavelength exhibiting specific light absorption, and a near-infrared light source that emits light at at least one wavelength λ2 that is difficult to be absorbed by the substance,
An infinite objective lens or a finite objective lens,
A beam splitter for separating incident light or reflected light;
When the measurement positions at different depths from the surface of the biological tissue are the normal focal plane and the non-normal focal plane, the reflected light intensity from the normal focal plane and the non-normal focal plane can be moved in the optical axis direction. A confocal optical system having an image lens and a pinhole, and an infinite objective lens or a lens arranged between the finite objective lens and the confocal optical system, movable in the direction of the optical axis, or exchangeable Means for focusing by an optical system capable of switching a focal position composed of lens groups having different focal lengths;
A near-infrared detector capable of identifying near-infrared intensity of wavelength λ1, and a near-infrared detector capable of identifying near-infrared intensity of wavelength λ2,
The correction coefficient calculated by the intensity ratio (regular reflected light intensity / non-regular reflected light intensity) between the reflected light intensity of the normal focal plane and the reflected light intensity of the non-normal focal plane at the correction wavelength λ2 is measured as described above. Using the corrected non-regular reflected light intensity obtained by multiplying the reflected light intensity of the non-normal focal plane at the wavelength λ1 and the reflected light intensity of the normal focal plane measured at the measurement wavelength λ1, Lambert In accordance with Beer's law, an arithmetic processing means for calculating the content of a substance present in a region sandwiched between the normal focal plane and the non-normal focal plane ;
An apparatus for measuring the amount of a substance present in a living tissue, comprising:
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