JP2932644B2 - Method and apparatus for measuring cytochrome oxidase - Google Patents
Method and apparatus for measuring cytochrome oxidaseInfo
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- JP2932644B2 JP2932644B2 JP23137890A JP23137890A JP2932644B2 JP 2932644 B2 JP2932644 B2 JP 2932644B2 JP 23137890 A JP23137890 A JP 23137890A JP 23137890 A JP23137890 A JP 23137890A JP 2932644 B2 JP2932644 B2 JP 2932644B2
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- hemoglobin
- absorbance
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Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は近赤外領域の特定波長光を用いて生体内のチ
トクロムオキシダーゼ（cytaa3）の酸化還元状態を無侵
襲に測定する方法とその装置に関するものである。The present invention relates to a method for non-invasively measuring the oxidation-reduction state of cytochrome oxidase (cytaa 3 ) in a living body using light having a specific wavelength in the near-infrared region and the method. It concerns the device.
（従来の技術） 近赤外領域の特定波長光を生体に照射し、その透過光
又は散乱・反射光を測定して、その吸光度の経時変化か
らチトクロムオキシダーゼの酸化還元状態を測定する方
法が知られている（Adv.Exp.Med.Biol.,Vol.248,pp.63
−68（1989）参照）。その方法では、チトクロムオキシ
ダーゼの酸化還元状態による吸光度変化を受けにくい波
長域（700〜780nm）の特定波長と、受けやすい波長域
（780〜900nm）の特定波長での吸光度変化の測定を組み
合わせて、チトクロムオキシダーゼの酸化還元状態を演
算により計測している。(Prior art) A method of irradiating a living body with light having a specific wavelength in the near-infrared region, measuring the transmitted light or scattered / reflected light, and measuring the redox state of cytochrome oxidase from the change with time of the absorbance is known. (Adv. Exp. Med. Biol., Vol. 248, pp. 63
-68 (1989)). The method combines the measurement of the absorbance change at a specific wavelength in the wavelength range (700-780 nm) that is less susceptible to absorbance change due to the oxidation-reduction state of cytochrome oxidase and the specific wavelength in the susceptible wavelength range (780-900 nm) The redox state of cytochrome oxidase is measured by calculation.
また、本発明者はチトクロムオキシダーゼの酸化還元
状態による吸光度変化を受けにくい波長域においては、
特定の複数波長での吸光度の経時変化からヘモグロビン
の酸素動態を測定する方法をすでに提案している（特願
昭63−248833号参照）。In addition, the present inventor, in a wavelength range that is less susceptible to absorbance change due to the redox state of cytochrome oxidase
A method for measuring the oxygen dynamics of hemoglobin from the change over time in absorbance at a plurality of specific wavelengths has already been proposed (see Japanese Patent Application No. 63-248833).
（発明が解決しようとする課題） 光源としては特定発振波長の半導体レーザを複数種類
組み合わせて用いる方法や、連続波長の光源と分光器を
組み合わせて所定の波長を得る方法等があるが、特に光
源として半導体レーザを用いる場合には、発振波長の制
約から所望の波長を選択できない場合がある。より具体
的に述べると、invivoで生体を計測をする場合には、生
体組織での減光度がかなり大きいため、光源出力をある
程度強くする必要がある。しかし、現在の段階では780n
m以下の波長域で高出力の半導体レーザを入手すること
は困難である。(Problems to be Solved by the Invention) As a light source, there are a method using a combination of a plurality of types of semiconductor lasers having a specific oscillation wavelength, a method of obtaining a predetermined wavelength by combining a light source having a continuous wavelength and a spectroscope, and the like. When a semiconductor laser is used, a desired wavelength may not be selected due to the limitation of the oscillation wavelength. More specifically, when measuring a living body in vivo, it is necessary to increase the output of the light source to some extent because the degree of dimming in the living tissue is quite large. But at the current stage 780n
It is difficult to obtain a high-power semiconductor laser in a wavelength range of less than m.
本発明は高出力半導体レーザの入手が容易な780nm以
上の波長域、すなわちチトクロムオキシダーゼの酸化還
元状態変化に伴う吸光度変化が生じる近赤外領域におい
てのみ吸光度の経時変化を測定することにより選択波長
に制限を受けることなくチトクロムオキシダーゼの酸化
還元状態を計測することのできる方法と、そのための装
置を提供すること目的とするものである。The present invention provides a high-output semiconductor laser in a wavelength range of 780 nm or more, that is, in the near-infrared region where the change in the absorbance associated with the change in the oxidation-reduction state of cytochrome oxidase is measured, and the change over time in the absorbance is measured. It is an object of the present invention to provide a method capable of measuring the oxidation-reduction state of cytochrome oxidase without restriction, and an apparatus therefor.
（課題を解決するための手段） 本発明の測定方法では、以下の工程（Ａ）から（Ｃ）
を用いてチトクロムオキシダーゼの変動量を測定する。(Means for Solving the Problems) In the measuring method of the present invention, the following steps (A) to (C)
Is used to measure the amount of change in cytochrome oxidase.
（Ａ）ヘモグロビンの酸素化−脱酸素化に伴う吸光度変
化とチトクロムオキシダーゼの酸化還元状態変化に伴う
吸光度変化がともに生ずる近赤外領域において、２組の
異なる波長群の光を生体組織に照射して各波長での吸光
度変化を測定する工程、 （Ｂ）各波長群について吸光度変化が全てヘモグロビン
の酸素化−脱酸素化に依存すると仮定し、吸光係数とし
て各波長での酸素化型ヘモグロビンの吸光係数及び脱酸
素化型ヘモグロビンの吸光係数のみを用いてヘモグロビ
ン量変動を算出する工程、 （Ｃ）これら２組の波長群のヘモグロビン量変動算出値
の差からチトクロムオキシダーゼの変動量を算出する工
程。(A) In the near-infrared region where both the change in absorbance due to oxygenation and deoxygenation of hemoglobin and the change in absorbance due to change in the oxidation-reduction state of cytochrome oxidase are performed, living tissue is irradiated with light of two different wavelength groups. (B) assuming that the change in absorbance at each wavelength group depends on oxygenation-deoxygenation of hemoglobin, and as an extinction coefficient, the absorbance of oxygenated hemoglobin at each wavelength. Calculating the hemoglobin amount fluctuation using only the coefficient and the absorption coefficient of deoxygenated hemoglobin; and (C) calculating the fluctuation amount of cytochrome oxidase from the difference between the calculated hemoglobin fluctuation values of these two wavelength groups.
また、本発明のチトクロムオキシダーゼ測定装置は、
ヘモグロビンの酸素化−脱酸素化に伴う吸光度変化とチ
トクロムオキシダーゼの酸化還元状態変化に伴う吸光度
変化がともに生ずる近赤外領域において、２組の異なる
波長群の光を生体組織に順次照射して各波長での吸光度
変化を測定する測定系と、各波長群について吸光度変化
が全てヘモグロビンの酸素化−脱酸素化に依存すると仮
定し、吸光係数として各波長での酸素化型ヘモグロビン
の吸光係数及び脱酸素化型ヘモグロビンの吸光係数のみ
を用いてヘモグロビン量変動を算出し、これら２組の波
長群のヘモグロビン量変動算出値の差からチトクロムオ
キシダーゼの変動量を算出する演算部とを備えている。Further, the cytochrome oxidase measurement device of the present invention,
In the near-infrared region where both the change in the absorbance due to the oxygenation-deoxygenation of hemoglobin and the change in the absorbance due to the change in the oxidation-reduction state of cytochrome oxidase occur, living tissue is sequentially irradiated with light of two different wavelength groups. Assuming that the absorbance change for each wavelength group depends on the oxygenation-deoxygenation of hemoglobin, and the measurement system that measures the absorbance change at each wavelength, the extinction coefficient and desorption rate of oxygenated hemoglobin at each wavelength are assumed as extinction coefficients. A calculation unit for calculating the variation in hemoglobin amount using only the extinction coefficient of oxygenated hemoglobin, and calculating the variation amount of cytochrome oxidase from the difference between the calculated values of the variation in hemoglobin amount of these two wavelength groups.
（作用） チトクロムオキシダーゼの酸化還元状態変化に伴う吸
光度変化が生じる波長においては、ヘモグロビンの酸素
化・脱酸素化によっても吸光度変化が生じるため、吸光
度変化はヘモグロビンの吸光度変化とチトクロムオキシ
ダーゼの吸光度変化との和になる。前述の引用文献及び
特許出願にも示されているように、ある波長における吸
光度変化は次の式で表される。(Action) At a wavelength where the absorbance change accompanying the change in the oxidation-reduction state of cytochrome oxidase occurs, the absorbance change also occurs due to the oxygenation and deoxygenation of hemoglobin. Therefore, the absorbance change is the change in absorbance of hemoglobin and the change in absorbance of cytochrome oxidase. The sum of As shown in the above cited documents and patent applications, the change in absorbance at a certain wavelength is represented by the following equation.
ΔＡλｎ＝knΔ〔HbO2〕＋kn′Δ〔Hb〕＋kn″Δ〔cyta
a3〕 ……（１） この（１）式の右辺第３項がないもの仮定した場合、
つまり吸光度変化は全てヘモグロビンの酸素化−脱酸素
化状態の変化に伴うものであると仮定した場合、酸素化
型ヘモグロビン変動Δ〔HbO2〕又は脱酸素化型ヘモグロ
ビン変動Δ〔Hb〕は前述の特許出願に述べられているよ
うに、 Δ〔HbO2〕＝｛（k2′−k3′）ΔA1−（k1′−k3′）Δ
A2＋（k1′−k2′）ΔA3｝/K ……（２） Δ〔Hb〕＝｛−（k2−k3）ΔA1＋（k1−k3）ΔA2−（k1
−k2）ΔA3｝/K ……（３） として算出することができる。ここで、ΔA1，ΔA2，Δ
A3は３波長λ1，λ2，λ3をそれぞれ生体組織に直接照
射して測定した吸光度変化、k1，k2，k3はそれぞれ波長
λ1，λ2，λ3をそれぞれ生体組織に直接照射して測定
された吸光度変化、k1，k2，k3における酸素化型ヘモグ
ロビンの吸光係数、k1′，k2′，k3′はそれぞれ波長λ
1，λ2，λ3における脱酸素化型ヘモグロビンの吸光係
数、Ｋ＝（k1−k3）（k2′−k3′）−（k2−k3）（k1′
−k3′）である。ΔAλn = knΔ [HbO 2 ] + kn′Δ [Hb] + kn ″ Δ [cyta
a 3 ] ... (1) Assuming that there is no third term on the right side of equation (1),
In other words, assuming that the change in absorbance is all due to the change in the oxygenated / deoxygenated state of hemoglobin, the oxygenated hemoglobin fluctuation Δ [HbO 2 ] or the deoxygenated hemoglobin fluctuation Δ [Hb] is as described above. As stated in the patent application, Δ [HbO 2 ] = ｛(k 2 ′ −k 3 ′) ΔA 1 − (k 1 ′ −k 3 ′) Δ
A 2 + (k 1 ′ −k 2 ′) ΔA 3 ｝ / K (2) Δ [Hb] = ｛− (k 2 −k 3 ) ΔA 1 + (k 1 −k 3 ) ΔA 2 − ( k 1
−k 2 ) ΔA 3 ｝ / K (3) Here, ΔA 1 , ΔA 2 , Δ
A 3 is a change in absorbance measured by directly irradiating the living tissue with three wavelengths λ 1 , λ 2 , and λ 3 , and k 1 , k 2 , and k 3 are wavelengths λ 1 , λ 2 , and λ 3 respectively. , The change in absorbance measured by directly irradiating, the absorption coefficient of oxygenated hemoglobin at k 1 , k 2 , and k 3 , and k 1 ′, k 2 ′, and k 3 ′ are wavelengths λ, respectively.
Extinction coefficient of deoxygenated hemoglobin at 1 , λ 2 , λ 3 , K = (k 1 −k 3 ) (k 2 ′ −k 3 ′) − (k 2 −k 3 ) (k 1 ′)
−k 3 ′).
これらのヘモグロビン変動の式（２），（３）はチト
クロムオキシダーゼの変化分が誤差となるが、逆にこの
ことを利用して選択波長の違いによるチトクロムオキシ
ダーゼの吸光係数の差からこれに依存するパラメータを
算出することができる。チトクロムオキシダーゼの酸化
還元状態変化に伴う吸光度変化がないものとしてある特
定波長の組合せで求めた酸素化型ヘモグロビン変化量Δ
〔HbO2〕ａと、別の特定波長の組合せで求めた酸素化型
ヘモグロビン変化量Δ〔HbO2〕ｂを算出し、それらのゲ
インを合わせた後に減算して得られる次式の新しいパラ
メータＮ［cytaa3］はチトクロムオキシダーゼの酸化還
元状態変化に比例する量となる。In the formulas (2) and (3) for hemoglobin fluctuation, the amount of change in cytochrome oxidase causes an error. Conversely, this is utilized to depend on the difference in the absorption coefficient of cytochrome oxidase due to the difference in the selected wavelength. Parameters can be calculated. Oxygenated hemoglobin change Δ determined by a combination of specific wavelengths assuming that there is no change in absorbance due to change in the oxidation-reduction state of cytochrome oxidase
[HbO 2 ] a and the oxygenated hemoglobin variation Δ [HbO 2 ] b obtained by combining another specific wavelength are calculated, and after adjusting their gains, a new parameter N of the following equation is obtained. [Cytaa 3 ] is an amount proportional to the change in the redox state of cytochrome oxidase.
Δ［cytaa3］≒Ｎ［cytaa3］ ＝Δ〔HbO2〕ａ−ＫΔ〔HbO2〕ｂ ラットの吸入ガスの酸素濃度を変えた際の脳内酸素化
型ヘモグロビンとチトクロムオキシダーゼの挙動を調べ
た実験によれば、チトクロムオキシダーゼは正常な状態
ではほとんど酸化されているが、吸気ガスの酸素濃度が
減少して酸素化型ヘモグロビンが15％以下になると徐々
に還元されはじめ、オキシヘモグロビンが５％以下にな
ると大幅に還元されることがわかっている。Δ [cytaa 3 ] ≒ N [cytaa 3 ] = Δ [HbO 2 ] a-KΔ [HbO 2 ] b The behavior of oxygenated hemoglobin and cytochrome oxidase in the brain when the oxygen concentration of the inhaled gas of the rat was changed was investigated. According to the experiment, cytochrome oxidase was almost oxidized under normal conditions, but when the oxygen concentration of the inspired gas decreased and oxygenated hemoglobin became 15% or less, it gradually began to be reduced, and oxyhemoglobin became 5%. It is known that the amount is greatly reduced when the amount of water is reduced below.
また、ラット頭部の近赤外吸収スペクトルの測定結果
によれば、780nm以下の波長ではチトクロムオキシダー
ゼの酸化還元状態変化に伴う吸光度変化はなく、ヘモグ
ロビンの酸素化−脱酸素化に伴う吸光度変化のみが観測
され、780nmより長波長側においてはチトクロムオキシ
ダーゼの酸化還元状態変化に伴う吸光度変化と、ヘモグ
ロビンの酸素化−脱酸素化に伴う吸光度変化がともに観
測される。In addition, according to the measurement results of the near-infrared absorption spectrum of the rat head, at wavelengths of 780 nm or less, there was no change in absorbance due to the change in the oxidation-reduction state of cytochrome oxidase, only the change in absorbance due to oxygenation-deoxygenation of hemoglobin. On the longer wavelength side than 780 nm, both the change in the absorbance due to the change in the redox state of cytochrome oxidase and the change in the absorbance due to the oxygenation-deoxygenation of hemoglobin are observed.
前記（２）式により酸素化型ヘモグロビン変動量を算
出する例について説明する。An example in which the oxygenated hemoglobin fluctuation amount is calculated by the equation (2) will be described.
チトクロムオキシダーゼの酸化還元状態変化に伴う吸
光度変化を受ける波長（λ1，λ2，λ3）での吸光度変
化から算出した酸素化型ヘモグロビン変動量をΔ〔Hb
O2〕123とし、やはりチトクロムオキシダーゼの酸化還
元状態変化に伴う吸光度変化を受ける他の波長（λ4，
λ5，λ6）での吸光度変化から算出した酸素化型ヘモグ
ロビン変動量をΔ〔HbO2〕456とする。The change in oxygenated hemoglobin calculated from the change in absorbance at wavelengths (λ 1 , λ 2 , λ 3 ) that undergoes a change in absorbance associated with a change in the oxidation-reduction state of cytochrome oxidase is Δ [Hb
O 2 ] 123, and other wavelengths (λ 4 ,
The change in oxygenated hemoglobin calculated from the change in absorbance at λ 5 , λ 6 ) is Δ [HbO 2 ] 456 .
チトクロムオキシダーゼが殆ど変化しない領域、すな
わちラットの場合であれば吸入ガス中の酸素濃度の高い
状態では、吸光度変化はヘモグロビンのみに依存すると
考えてよく、Δ〔HbO2〕123とΔ〔HbO2〕456は同じ波形
となる。ただし絶対値は異なる。このとき各時刻での変
化量Δ〔HbO2〕123を横軸にとり、Δ〔HbO2〕456を縦軸
にとってプロットすると、第１図（Ａ）のように直線と
なる。この傾きをＫとして Ｎ［cytaa3］＝Δ〔HbO2〕456−ＫΔ〔HbO2〕123 というパラメータＮ［cytaa3］を考えると、その波形は
第１図（Ｃ）に示されるようにフラットになり、０を示
す。In a region where cytochrome oxidase hardly changes, that is, in the case of a rat, in a state where the oxygen concentration in the inhaled gas is high, the change in absorbance may be considered to depend only on hemoglobin, and Δ [HbO 2 ] 123 and Δ [HbO 2 ] 456 has the same waveform. However, the absolute values are different. At this time, when the variation Δ [HbO 2 ] 123 at each time is plotted on the horizontal axis and Δ [HbO 2 ] 456 is plotted on the vertical axis, a straight line as shown in FIG. 1A is obtained. Taking this slope as K and considering a parameter N [cytaa 3 ] of N [cytaa 3 ] = Δ [HbO 2 ] 456 −KΔ [HbO 2 ] 123 , the waveform is flat as shown in FIG. , Indicating 0.
次に、チトクロムオキシダーゼも途中（時刻t1）から
還元され始めたとすると、Δ〔HbO2〕123とΔ〔HbO2〕
456との間に傾きＫの比例関係はなくなり、例えば第１
図（Ｂ）のようにずれてくる。この時刻t1以降ではパラ
メータＮ［cytaa3］の値は、第１図（Ｄ）に示されるよ
うに、チトクロムオキシダーゼによる吸光度変化分のた
めにずれを生じており、これがすなわちチトクロムオキ
シダーゼの酸化還元状態を反映したパラメータとなる。
これによってチトクロムオキシダーゼの算出法がわから
なくても、ヘモグロビンの算出法さえわかればチトクロ
ムオキシダーゼの酸化還元状態の変化をモニタすること
ができる。Next, assuming that cytochrome oxidase also starts to be reduced halfway (time t 1 ), Δ [HbO 2 ] 123 and Δ [HbO 2 ]
There is no longer a proportional relationship of the slope K with 456 ,
It shifts as shown in FIG. The time value t 1 parameter N [cytaa 3] is later, as shown in FIG. 1 (D), and deviated for absorbance change due cytochrome oxidase, which is namely redox cytochrome oxidase The parameters reflect the status.
Thus, even if the calculation method of cytochrome oxidase is not known, the change in the oxidation-reduction state of cytochrome oxidase can be monitored as long as the calculation method of hemoglobin is known.
３波長演算によりヘモグロビン変動量を算出するとき
は、その式は（１）式から ΔＡλｎ−kn″Δ〔cytaa3〕＝knΔ〔HbO2〕＋kn′Δ
〔Hb〕 （ｎ＝1,2,3） となる。この式から酸素化型ヘモグロビンの変動量を解
くと、 Δ〔HbO2〕＝（An1ΔＡλn1＋An2ΔＡλn2＋An3ΔＡλn
3）＋BnΔ〔cytaa3〕 という形になる。左辺は実際の酸素化型ヘモグロビン変
動量、右辺第１項は見かけの酸素化型ヘモグロビン変動
量、右辺第２項はチトクロムオキシダーゼ吸光度変化に
よる酸素化型ヘモグロビン測定誤差である。左辺は波長
選択が違えば値が違ってくるが、実際は同じ変化量を示
しているので、係数Ｋを乗じた後、辺々引き算をすれば
チトクロムオキシダーゼの変化量と吸光度変化量の項の
みが残る。すなわち吸光度変化からチトクロムオキシダ
ーゼ変化量を算出することができる。When calculating the hemoglobin fluctuation amount by the three-wavelength calculation, the equation is given by the following equation (1): ΔAλn-kn ″ Δ [cytaa 3 ] = knΔ [HbO 2 ] + kn′Δ
[Hb] (n = 1, 2, 3). By solving the variation of oxygenated hemoglobin from this equation, Δ [HbO 2 ] = (An 1 ΔAλn 1 + An 2 ΔAλn 2 + An 3 ΔAλn
3 ) + BnΔ [cytaa 3 ] The left side is the actual fluctuation amount of oxygenated hemoglobin, the first term on the right side is the apparent fluctuation amount of oxygenated hemoglobin, and the second term on the right side is the measurement error of oxygenated hemoglobin due to the change in the absorbance of cytochrome oxidase. The values on the left side will differ if the wavelength selection is different, but they actually show the same amount of change, so after multiplying by the coefficient K and subtracting each side, only the terms of the amount of change in cytochrome oxidase and the amount of change in absorbance are obtained. Remains. That is, the change in cytochrome oxidase can be calculated from the change in absorbance.
請求項１ではヘモグロビンの酸素化−脱酸素化に伴う
吸光度変化とチトクロムオキシダーゼの酸化還元状態に
伴う吸光度変化がともに生ずる近赤外領域の２組の波長
ペアを選択しているが、１組をチトクロムオキシダーゼ
の酸化還元状態による吸光度変化がない波長域（700nm
〜780nm）にすればより顕著な差を認めることができ
る。In claim 1, two wavelength pairs in the near-infrared region where both a change in absorbance due to oxygenation-deoxygenation of hemoglobin and a change in absorbance due to the redox state of cytochrome oxidase are selected, but one set is selected. The wavelength range where the absorbance does not change due to the redox state of cytochrome oxidase (700 nm
780 nm), a more remarkable difference can be recognized.
（実施例） 第２図は一実施例の測定装置を表わす。(Embodiment) FIG. 2 shows a measuring apparatus of one embodiment.
２−１〜２−６はそれぞれ特定の波長λ1〜λ6のレー
ザ光を発振するレーザダイオードであり、３個ずつの組
が２組設けられている。発振波長λ1〜λ6は780nm以上
に設定されている。レーザダイオード２−１〜２−３は
駆動回路４によって順次切り替えて発振させられる。駆
動回路４はCPU6によって制御される。８は測定対象とし
ての生体組織であり、レーザダイオード２−１〜２−６
からのレーザビームが照射用光ガイド10によって生体組
織８に導かれる。光ガイド10は例えば直径5mmの光ファ
イバ束である。12は検出器である光電子増倍管であり、
生体組織８による透過光又は反射光が検出用光ガイド14
によって光電子増倍管12に導かれる。光ガイド14も例え
ば直径が5mmの光ファイバ束である。Reference numerals 2-1 to 2-6 denote laser diodes that oscillate laser beams having specific wavelengths λ 1 to λ 6 , respectively, and two sets of three laser diodes are provided. The oscillation wavelengths λ 1 to λ 6 are set to 780 nm or more. The laser diodes 2-1 to 2-3 are sequentially switched and oscillated by the drive circuit 4. The drive circuit 4 is controlled by the CPU 6. Reference numeral 8 denotes a living tissue to be measured, and includes laser diodes 2-1 to 2-6.
Is guided to the living tissue 8 by the irradiation light guide 10. The light guide 10 is, for example, an optical fiber bundle having a diameter of 5 mm. 12 is a photomultiplier tube which is a detector,
The transmitted light or the reflected light by the living tissue 8 is converted into the detection light guide 14.
Is guided to the photomultiplier tube 12. The light guide 14 is also an optical fiber bundle having a diameter of 5 mm, for example.
16は光電子増倍管12の出力信号を増幅するプリアン
プ、18は増幅された信号をサンプルホールドするサンプ
ルホールド回路、20はサンプルホールド回路18の出力信
号を増幅する増幅器、22は増幅された信号電圧を周波数
に変換するV/F変換器であり、V/F変換器22の出力信号が
CPU6に入力されてカウントされる。16 is a preamplifier that amplifies the output signal of the photomultiplier tube 12, 18 is a sample and hold circuit that samples and holds the amplified signal, 20 is an amplifier that amplifies the output signal of the sample and hold circuit 18, and 22 is an amplified signal voltage. Is a V / F converter that converts the
Input to CPU 6 and counted.
CPU6はレーザダイオード２−１〜２−６の発振を制御
するとともに、各波長λ1〜λ6でのデータを取り込み、
経時吸光度変化量ΔA1〜ΔA6を算出する。算出した経時
吸光度変化量ΔA1〜ΔA6と予め測定されて設定された吸
光係数k1，k2，k3，k1′，k2′，k3′とから酸素化型ヘ
モグロビン量変動Δ〔HbO2〕123とΔ〔HbO2〕456を算出
し、これをもとにしてパラメータ Ｎ［cytaa3］＝Δ〔HbO2〕456−ＫΔ〔HbO2〕123 を算出する。したがって、CPU6はヘモグロビン量変動算
出値の差からチトクロムオキシダーゼの変動量を算出す
る演算部の機能を実現している。測定系24は第２図で鎖
線で囲まれた部分に該当する。The CPU 6 controls the oscillations of the laser diodes 2-1 to 2-6, fetches data at each wavelength λ 1 to λ 6 ,
The amount of change in absorbance with time ΔA 1 to ΔA 6 is calculated. From the calculated change in absorbance with time ΔA 1 to ΔA 6 and the previously measured absorption coefficients k 1 , k 2 , k 3 , k 1 ′, k 2 ′, and k 3 ′, the change in oxygenated hemoglobin amount Δ [HbO 2 ] 123 and Δ [HbO 2 ] 456 are calculated, and the parameter N [cytaa 3 ] = Δ [HbO 2 ] 456 −KΔ [HbO 2 ] 123 is calculated based on this. Therefore, the CPU 6 implements the function of a calculation unit that calculates the amount of change in cytochrome oxidase from the difference between the calculated values of hemoglobin change. The measurement system 24 corresponds to a portion surrounded by a chain line in FIG.
第２図においてCPU6には入出力部32を介して、この装
置を操作したり吸光係数を入力するためのキーボード3
4、測定値などを表示する液晶ディスプレイ36、測定結
果を出力するレコーダ38、異常を知らせる警報装置40な
どが接続されている。In FIG. 2, a keyboard 3 for operating the apparatus and inputting an extinction coefficient is provided to the CPU 6 via an input / output unit 32.
4. A liquid crystal display 36 for displaying a measured value, a recorder 38 for outputting a measurement result, an alarm device 40 for notifying an abnormality, and the like are connected.
次に、本実施例における吸光度測定動作について説明
する。Next, the absorbance measurement operation in this embodiment will be described.
第３図はCPU6が測定値を取り込み、ダーク補正をする
までのタイムチャートである。図には簡単のために、３
波長で測定を行なうように説明しているが、第２図の実
施例は６波長での測定であり、単にレーザダイオードの
数が増えるだけと考えればよい。FIG. 3 is a time chart from when the CPU 6 takes in the measured values and performs dark correction. For simplicity, 3
Although it is described that the measurement is performed at the wavelength, the embodiment of FIG. 2 is a measurement at six wavelengths, and it can be considered that the number of laser diodes simply increases.
第３図で、A,B,Cはそれぞれ波長λ1，λ2，λ3のレー
ザダイオード２−１〜２−３の駆動パルス、Ｄは積分パ
ルス、Ｅはサンプリングパルス、Ｆはリセットパルス、
Ｇは光電子増倍管12の出力信号、Ｈは波長λ1のチャネ
ルのサンプルホールド前の出力信号である。他のチャネ
ルについても同様の出力信号Ｈが得られる。Ｓλ1は信
号レベル、Ｄλ1はダークレベルである。ＩはＳλ1−Ｄ
λ1であり、これによって真の信号レベルを得ることが
できる。In FIG. 3, A, B, and C denote drive pulses for the laser diodes 2-1 to 2-3 of wavelengths λ 1 , λ 2 , and λ 3 , D denotes an integration pulse, E denotes a sampling pulse, F denotes a reset pulse,
G is the output signal of the photomultiplier tube 12, H is the sample-hold prior to the output signal of the wavelength lambda 1 of the channel. Similar output signals H are obtained for other channels. Sλ 1 is a signal level, and Dλ 1 is a dark level. I is Sλ 1 -D
a lambda 1, whereby it is possible to obtain a true signal level.
（発明の効果） 本発明によれば、ヘモグロビンの酸素化−脱酸素化に
伴う吸光度変化とチトクロムオキシダーゼの酸化還元状
態変化に伴う吸光度変化がともに生ずる近赤外領域にお
いて、ヘモグロビン量変動値からチトクロムオキシダー
ゼの酸化還元状態を測定するので、ヘモグロビンに比べ
て吸光度変化の小さいチトクロムオキシダーゼの酸化還
元状態を光源波長の選択の制約を受けることなく、無侵
襲に測定することが可能になる。(Effects of the Invention) According to the present invention, in the near-infrared region where both the change in the absorbance due to the oxygenation and deoxygenation of hemoglobin and the change in the absorbance due to the change in the oxidation-reduction state of cytochrome oxidase occur, the change in the amount of cytochrome from the amount of hemoglobin Since the redox state of oxidase is measured, the redox state of cytochrome oxidase having a smaller change in absorbance than hemoglobin can be measured noninvasively without being restricted by the selection of the light source wavelength.
第１図は本発明の測定原理を説明する図、第２図は測定
装置の一実施例を示すブロック図、第３図は一実施例の
検出動作を示すタイムチャートである。 ２−１〜２−６……レーザダイオード、６……CPU、８
……生体組織、24……測定系。FIG. 1 is a view for explaining the measurement principle of the present invention, FIG. 2 is a block diagram showing one embodiment of a measuring apparatus, and FIG. 3 is a time chart showing a detection operation of one embodiment. 2-1 to 2-6: laser diode, 6: CPU, 8
…… living tissue, 24 …… measurement system.
フロントページの続き (56)参考文献 特開 昭63−275323（ＪＰ，Ａ) 特開 平３−68336（ＪＰ，Ａ) 特開 昭62−41639（ＪＰ，Ａ) 特開 昭61−11614（ＪＰ，Ａ) 特開 昭48−101195（ＪＰ，Ａ) (58)調査した分野(Int.Cl.6，ＤＢ名) G01N 21/00 - 21/01 G01N 21/17 - 21/61 Continuation of the front page (56) References JP-A-63-275323 (JP, A) JP-A-3-68336 (JP, A) JP-A-62-141639 (JP, A) JP-A-61-11614 (JP) , A) JP-A-48-101195 (JP, A) (58) Fields investigated (Int. Cl. 6 , DB name) G01N 21/00-21/01 G01N 21/17-21/61
Claims (2)
クロムオキシダーゼの変動量を測定する方法。 （Ａ）ヘモグロビンの酸素化−脱酸素化に伴う吸光度変
化とチトクロムオキシダーゼの酸化還元状態変化に伴う
吸光度変化がともに生ずる近赤外領域において、２組の
異なる波長群の光を生体組織に照射して各波長での吸光
度変化を測定する工程、 （Ｂ）各波長群について吸光度変化が全てヘモグロビン
の酸素化−脱酸素化に依存すると仮定し、吸光係数とし
て各波長での酸素化型ヘモグロビンの吸光係数及び脱酸
素化型ヘモグロビンの吸光係数のみを用いてヘモグロビ
ン量変動を算出する工程、 （Ｃ）これら２組の波長群のヘモグロビン量変動算出値
の差からチトクロムオキシダーゼの変動量を算出する工
程。1. A method for measuring the amount of change in cytochrome oxidase using the following steps (A) to (C). (A) In the near-infrared region where both the change in absorbance due to oxygenation and deoxygenation of hemoglobin and the change in absorbance due to change in the oxidation-reduction state of cytochrome oxidase are performed, living tissue is irradiated with light of two different wavelength groups. (B) assuming that the change in absorbance at each wavelength group depends on oxygenation-deoxygenation of hemoglobin, and as an extinction coefficient, the absorbance of oxygenated hemoglobin at each wavelength. Calculating the hemoglobin amount fluctuation using only the coefficient and the absorption coefficient of deoxygenated hemoglobin; and (C) calculating the fluctuation amount of cytochrome oxidase from the difference between the calculated hemoglobin fluctuation values of these two wavelength groups.
光度変化とチトクロムオキシダーゼの酸化還元状態変化
に伴う吸光度変化がともに生ずる近赤外領域において、
２組の異なる波長群の光を生体組織に順次照射して各波
長での吸光度変化を測定する測定系と、各波長群につい
て吸光度変化が全てヘモグロビンの酸素化−脱酸素化に
依存すると仮定し、吸光係数として各波長での酸素化型
ヘモグロビンの吸光係数及び脱酸素化型ヘモグロビンの
吸光係数のみを用いてヘモグロビン量変動を算出し、こ
れら２組の波長群のヘモグロビン量変動算出値の差から
チトクロムオキシダーゼの変動量を算出する演算部とを
備えたチトクロムオキシダーゼ測定装置。2. In the near-infrared region where both a change in absorbance associated with oxygenation and deoxygenation of hemoglobin and a change in absorbance associated with a change in the oxidation-reduction state of cytochrome oxidase occur.
Assume that a measuring system for sequentially irradiating living tissue with light of two different wavelength groups and measuring the change in absorbance at each wavelength, and that the change in absorbance for each wavelength group all depends on oxygenation-deoxygenation of hemoglobin. Calculate the hemoglobin amount variation using only the absorption coefficient of oxygenated hemoglobin and the absorption coefficient of deoxygenated hemoglobin at each wavelength as the extinction coefficient. From the difference between the calculated values of the hemoglobin amount variation of these two wavelength groups, A cytochrome oxidase measurement device, comprising: a calculation unit for calculating a fluctuation amount of cytochrome oxidase.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23137890A JP2932644B2 (en) | 1990-08-31 | 1990-08-31 | Method and apparatus for measuring cytochrome oxidase |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23137890A JP2932644B2 (en) | 1990-08-31 | 1990-08-31 | Method and apparatus for measuring cytochrome oxidase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04110751A JPH04110751A (en) | 1992-04-13 |
| JP2932644B2 true JP2932644B2 (en) | 1999-08-09 |
Family
ID=16922683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23137890A Expired - Lifetime JP2932644B2 (en) | 1990-08-31 | 1990-08-31 | Method and apparatus for measuring cytochrome oxidase |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2932644B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2563012A1 (en) | 2011-08-25 | 2013-02-27 | Sony Corporation | Image sensor, imaging apparatus and live body imaging apparatus |
| WO2014017314A1 (en) | 2012-07-24 | 2014-01-30 | ソニー株式会社 | Image pickup element, electronic device, and information processing device |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3577335B2 (en) * | 1993-06-02 | 2004-10-13 | 浜松ホトニクス株式会社 | Scattering absorber measurement method and device |
| JP3433498B2 (en) * | 1993-06-02 | 2003-08-04 | 浜松ホトニクス株式会社 | Method and apparatus for measuring internal information of scattering medium |
-
1990
- 1990-08-31 JP JP23137890A patent/JP2932644B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2563012A1 (en) | 2011-08-25 | 2013-02-27 | Sony Corporation | Image sensor, imaging apparatus and live body imaging apparatus |
| WO2014017314A1 (en) | 2012-07-24 | 2014-01-30 | ソニー株式会社 | Image pickup element, electronic device, and information processing device |
| EP4057353A2 (en) | 2012-07-24 | 2022-09-14 | Sony Group Corporation | Imaging element, electronic device, and information processing device |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04110751A (en) | 1992-04-13 |
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