JPH01174940A - Measurement of hemoglobin - Google Patents
Measurement of hemoglobinInfo
- Publication number
- JPH01174940A JPH01174940A JP62336197A JP33619787A JPH01174940A JP H01174940 A JPH01174940 A JP H01174940A JP 62336197 A JP62336197 A JP 62336197A JP 33619787 A JP33619787 A JP 33619787A JP H01174940 A JPH01174940 A JP H01174940A
- Authority
- JP
- Japan
- Prior art keywords
- hemoglobin
- wavelength
- amount
- extinction coefficient
- wavelengths
- 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
Links
- 108010054147 Hemoglobins Proteins 0.000 title claims abstract description 80
- 102000001554 Hemoglobins Human genes 0.000 title claims abstract description 80
- 238000005259 measurement Methods 0.000 title description 11
- 238000006392 deoxygenation reaction Methods 0.000 claims abstract description 8
- 238000002835 absorbance Methods 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 22
- 230000008033 biological extinction Effects 0.000 claims description 20
- 230000003287 optical effect Effects 0.000 claims description 17
- 230000003595 spectral effect Effects 0.000 claims description 5
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 claims description 4
- 108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 claims description 4
- 238000000691 measurement method Methods 0.000 claims description 4
- 102000007513 Hemoglobin A Human genes 0.000 claims 1
- 108010085682 Hemoglobin A Proteins 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 17
- 239000008280 blood Substances 0.000 abstract description 17
- 238000006213 oxygenation reaction Methods 0.000 abstract 4
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 abstract 2
- 241000700159 Rattus Species 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 238000010586 diagram Methods 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000001678 irradiating effect Effects 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000013307 optical fiber Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 238000000411 transmission spectrum Methods 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 108010075027 Cytochromes a Proteins 0.000 description 1
- 101100453996 Rattus norvegicus Klk2 gene Proteins 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 108010036302 hemoglobin AS Proteins 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
Landscapes
- Investigating Or Analysing Materials By Optical Means (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
(6)産業上の利用分野
この発明はヘモグロビン測定法に関する。さらに詳しく
は近赤外領域の特定波長光を用いて生体血中のへモグ四
ビン量変動を直接測定する方法に関する。DETAILED DESCRIPTION OF THE INVENTION (6) Industrial Application Field This invention relates to a method for measuring hemoglobin. More specifically, the present invention relates to a method for directly measuring changes in the amount of hemoglyceride in the blood of a living body using light of a specific wavelength in the near-infrared region.
(ロ)従来の技術
従来血液中のヘモグロビン(以下Hbと略す)を測定す
る方法としては、生体外に血液を取シ出して測定する方
法と、生体外に血液を取シ出さず測定する方法とがある
。このうち後者の方法には。(B) Conventional technology Conventional methods for measuring hemoglobin (hereinafter abbreviated as Hb) in blood include a method in which blood is taken out of the living body and measured, and a method in which it is measured without taking blood out of the living body. There is. For the latter method.
皮膚を加温して動脈血化しその部位に酸素電極を貼りつ
けて経皮的に測定する方法、イヤーピースオキシメータ
やパルスオキシメータ等のオキシメータを用いた光学的
手法による方法、さらには反射光を用いてHbの酸素化
型(オキシ)−脱酸素化型(デオキシ)のスペクト、u
変化からヘモグロビン量の変動を測定する方法などが知
られている。There are two methods: percutaneous measurement by heating the skin to create arterial blood and attaching an oxygen electrode to the area; optical methods using oximeters such as earpiece oximeters and pulse oximeters; and methods using reflected light. The oxygenated (oxy)-deoxygenated (deoxy) spectrum of Hb, u
There are known methods for measuring fluctuations in the amount of hemoglobin based on changes in hemoglobin.
(ハ)発明が解決しようとする問題点
しかしながら、上記の経皮的に測定する方法では同一箇
所での長時間使用ができなく、得られる情報も末梢血管
のものだけであシ、臓器や頭部などの主要組織における
血液の状態を知ることはできない。(c) Problems to be solved by the invention However, the percutaneous measurement method described above cannot be used at the same location for a long time, and the information obtained can only be obtained from peripheral blood vessels. It is not possible to know the state of blood in major tissues such as the body.
一方オキシメータを用いる方法では、パルスオキシメー
タが普及しているが、指先の動脈に関する測定しかでき
ず9頭部や臓器等の生体主要組織における血液の直接測
定が不可能であシ、さらに静脈に関する測定ができない
。On the other hand, in the method of using an oximeter, pulse oximeters are widely used, but they can only measure blood in the arteries at the fingertips,9 and cannot directly measure blood in the main tissues of the body such as the head and internal organs. cannot be measured.
また上記スペク)/l/変化による方法では、血液量変
動による吸光度変化が上記オキシ−デオキシによる吸光
度変化にオーバーラツプしてくること。Furthermore, in the method based on spec)/l/ change, the absorbance change due to blood volume fluctuation overlaps with the absorbance change due to oxy-deoxy.
また主要組織ことに頭部の測定においてはチトクロムa
a3 (cytaas )の酸化還元状態変化に伴うス
ペクトル変動がオーバーラツプしてくること、さらに、
波長によって光路および光路長が異なってくることから
スペクトルに歪みを生ずるため、ヘモグロビン量に対応
するパラメータを容易に測定することができない等の問
題点がある。In addition, when measuring major tissues, especially the head, cytochrome a
The spectral fluctuations associated with changes in the redox state of a3 (cytaas) overlap;
Since the optical path and optical path length differ depending on the wavelength, distortion occurs in the spectrum, which poses problems such as the inability to easily measure parameters corresponding to the amount of hemoglobin.
この発明はかかる状況に鑑みなされたものであ92頭部
や臓器等の生体主要組織における血液中のヘモグロビン
量変動を、光学的手法によって生体から直接かつ連続的
に測定することが可能なヘモグロビン測定法を提供しよ
うとするものである。This invention was made in view of the above circumstances.92 Hemoglobin measurement that enables direct and continuous measurement of hemoglobin level fluctuations in blood in the main tissues of a living body such as the head and internal organs using an optical method. It seeks to provide law.
に)問題点を解決するための手段
かくしてこの発明によれば、実質的にヘモグロビンによ
る吸光度変化のみが生ずる波長領域において異なる特定
の2波長λ1およびλ2を選択し、これらの波長光を生
体組織に直接照射して各波長についての吸光度変化△A
1および△A2を測定し、この吸光度変化△A1および
ΔA2と、予め上記特定波長によって得られた吸光係数
5
kl: 波長λlにおける酸素化型ヘモグロビンの吸
光係数。B) Means for Solving the Problems Thus, according to the present invention, two different specific wavelengths λ1 and λ2 are selected in the wavelength range where only the absorbance change due to hemoglobin occurs, and light of these wavelengths is applied to living tissue. Absorbance change △A for each wavelength by direct irradiation
1 and ΔA2, and the absorbance changes ΔA1 and ΔA2 and the extinction coefficient 5 previously obtained at the above-mentioned specific wavelength. kl: Extinction coefficient of oxygenated hemoglobin at wavelength λl.
k’l: 波長λ!における脱酸素化型ヘモグロビン
の吸光係数。k'l: Wavelength λ! Extinction coefficient of deoxygenated hemoglobin in
k2二 波長λ2における酸素化型ヘモグロビンの吸
光係数。k22 Extinction coefficient of oxygenated hemoglobin at wavelength λ2.
k′2二 波長λ2における脱酸素化型ヘモグロビン
の吸光係数。k'22 Extinction coefficient of deoxygenated hemoglobin at wavelength λ2.
及び酸素化型ヘモグロビンと脱酸素化型ヘモグロビンの
等吸収点(波長λ3)における吸光係数に3とに基づい
て、上記照射光路中の酸素化型ヘモグロビン量変動、脱
酸素化型ヘモグロビン量変動および/または全ヘモグロ
ビン量変動を測定することを特徴とするヘモグロビン測
定法が提供される。and the extinction coefficient of 3 at the isosbestic point (wavelength λ3) of oxygenated hemoglobin and deoxygenated hemoglobin, the variation in the amount of oxygenated hemoglobin in the irradiation optical path, the variation in the amount of deoxygenated hemoglobin, and/or Alternatively, a hemoglobin measuring method is provided, which is characterized by measuring fluctuations in total hemoglobin amount.
この発明は生体組織に対して近赤外領域の波長を用いる
光学的手法において、 700nm以上の波長領域から
実質的にヘモグロビンによる吸光度変化のみが生ずる異
なる特定の2波長(λl、λ2)を選択して用いること
によシ、チトクロムaa3(cytaas)の酸化還元
レベル変化に伴う吸収スペクトル変動の影響を実質的に
排除し、生体主要組織ことに頭部等の血液中のヘモグロ
ビン(Hb)量変動を、該組織への上記波長光の直接照
射によシ無侵襲にモニタできうる方法であることを特徴
とする。This invention is an optical method that uses wavelengths in the near-infrared region for biological tissues, by selecting two specific different wavelengths (λl, λ2) from a wavelength region of 700 nm or more that cause only a change in absorbance due to hemoglobin. By using it as The present invention is characterized in that it is a method capable of non-invasively monitoring the tissue by directly irradiating the tissue with light of the above wavelength.
この発明の方法に用いられる2つの異なる特定の波長は
、実質的にヘモグロビンによる吸光度変化のみが生ずる
7QQnm以上の波長範囲から選択され、該波長範囲と
してはことに700〜780nmが好ましい。このこと
は後述する実施例の記載が参照される。また上記好まし
い波長範囲以外でも、測定対象の生体主要組織の吸入酸
素濃度が極端に小さく従ってチトクロムaa3の酸化還
元変化に伴うスベク)/7変動が無視できない状態以外
であれば。The two different specific wavelengths used in the method of the present invention are selected from a wavelength range of 7QQnm or more in which substantially only a change in absorbance due to hemoglobin occurs, and the wavelength range is particularly preferably 700 to 780 nm. Regarding this, reference will be made to the description of the embodiment described later. In addition, even outside the above-mentioned preferred wavelength range, the concentration of inhaled oxygen in the main tissue of the living body to be measured is extremely small, so long as the SBEK)/7 variation accompanying the redox change of cytochrome aa3 cannot be ignored.
該スペク)/L/変動はヘモグロビンの酸素化−脱酸素
化に伴うスペクトル変動に比べて無視できうるので、こ
の発明の方法が充分に適用できる。Since the spectrum)/L/ variation can be ignored compared to the spectrum variation accompanying oxygenation-deoxygenation of hemoglobin, the method of the present invention can be fully applied.
この発明の方法において上記波長範囲から選択される2
波長は、得られる吸光度の差が大きくかつ散乱等の波長
依存性の少ない組合わせが選択され1例えば700nm
と730nm 、 75Qnmと713Qnmの組合わ
せ等が好ましいが、これらに限定されない。In the method of this invention, two wavelengths are selected from the above wavelength range.
The wavelength is selected from a combination that provides a large difference in absorbance and less wavelength dependence due to scattering, etc.1, for example, 700 nm.
Combinations of 730nm, 75Qnm and 713Qnm, etc. are preferred, but are not limited to these.
また、酸素化型ヘモグロビンと脱酸素化型ヘモグロビン
の吸光度が同じになる点としては波長8051m付近で
ある。Further, the point at which the absorbance of oxygenated hemoglobin and deoxygenated hemoglobin become the same is around the wavelength of 8051 m.
この発明の方法において吸光度変化の測定は。In the method of this invention, the change in absorbance is measured.
轟該分野で通常用いられる分光光度計および検出器をそ
のまま用いることができる。ただし光源から検出器まで
の測定光路には、上記のごとく選択される特定の波長光
を測定対象の生体部位に直接照射できうるよう構成され
た測定部が設定される。Spectrophotometers and detectors commonly used in this field can be used as they are. However, in the measurement optical path from the light source to the detector, a measurement section configured to directly irradiate the specific wavelength light selected as described above to the biological part to be measured is set.
上記のごとき測定光路および測定部は光ファイバ等を用
いて構成することができる。The measurement optical path and measurement section as described above can be constructed using an optical fiber or the like.
この発明の方法は、ヘモグロビン量の変動と吸光度変化
との間に、ランベAz )−ベールの法則が成立する生
理範囲内で用いられる。すなわち、生体組織への特定波
長(λl、λ2.λ3)による照射光路(光路長:d)
中での求める各量変動:酸素化型ヘモグロビン(HbO
z )量変動、脱酸素化型ヘモグロビン(Hb )量変
動、全ヘモグロビン(IHb)量変動をそれぞれ順に△
(HbOz) 、△(Hb) 、△(IF(b:)とし
、さらにその組織の上記特定波長の照射光による吸光係
数すなわち、波長λ1における酸素化型ヘモグロビンの
吸光係数: k、 、同じく波長λ1における脱酸素化
型ヘモグロビンの吸光係数二に1′、波長λ2における
酸素化型ヘモグロビンの吸光係数:に2.同じく波長λ
2における脱酸素化型ヘモグロビンの吸光係数:に’、
酸素化型ヘモグロビンと脱酸素化型ヘモグロビンの吸光
度が同じになる点(波長λ3)におけるへそグロビンの
吸光係数二に3とした場合、各波長λ1.λ2またはλ
3による経時吸光度変化量ΔA1 +ΔA2さらに△A
3が
△A + = k+△(HbOz:] +kt’△(H
b ) −■△Ax = kz△(H
bOz:)+kz’△CHb) −■
△A3士kj△(HbOz) + ksΔ[:Hb)=
に3Δ〔II(b〕 −■で表される直線関係が
成立する生理範囲内である。The method of the present invention is used within a physiological range in which the Lambe-Az)-Beer law holds between fluctuations in the amount of hemoglobin and changes in absorbance. That is, the irradiation optical path (optical path length: d) with specific wavelengths (λl, λ2, λ3) to the biological tissue
Changes in each amount to be determined in: Oxygenated hemoglobin (HbO
z) Volume fluctuation, deoxygenated hemoglobin (Hb) volume fluctuation, and total hemoglobin (IHb) volume fluctuation are respectively △
(HbOz), △(Hb), △(IF(b:)), and the extinction coefficient of the tissue by the irradiation light of the above specific wavelength, that is, the extinction coefficient of oxygenated hemoglobin at wavelength λ1: k, , also at wavelength λ1 The extinction coefficient of deoxygenated hemoglobin at wavelength λ2 is 2:2.
Extinction coefficient of deoxygenated hemoglobin in 2: ni',
If the extinction coefficient of navel globin at the point (wavelength λ3) where the absorbance of oxygenated hemoglobin and deoxygenated hemoglobin are the same (wavelength λ3) is 2:3, then each wavelength λ1. λ2 or λ
Amount of change in absorbance over time due to 3 ΔA1 + ΔA2 and ΔA
3 is △A + = k+△(HbOz:] +kt'△(H
b) −■△Ax = kz△(H
bOz:)+kz'△CHb) -■
△A3shikj△(HbOz) + ksΔ[:Hb)=
is within the physiological range where a linear relationship expressed by 3Δ[II(b) -■ holds true.
上式■、■よシ、各量変動は
△〔H′bO2〕=(k2′△A+ −に+7胡)/
(ki k2′−kzk1’) −■△CH
b)=(k2△Ax−に1△A2)/(kzk1′−k
tk;) −■△(IF(b) = ((k
z’−kz)ム1−(k+’−kl)△んン(klk2
’−に2kl’) −■で表わすことができ、に3を
用いる事によシ次の式が算出される。According to the above formulas ■ and ■, each quantity fluctuation is △[H'bO2] = (k2'△A+ - +7 Hu)/
(ki k2'-kzk1') -■△CH
b) = (k2△Ax- to 1△A2)/(kzk1'-k
tk;) −■△(IF(b) = ((k
z'-kz)mu1-(k+'-kl)△nn (klk2
'-2kl') -■, and by using 3, the following equation is calculated.
ζこでkl’/に3 e k2’/に3は脱酸素化型ヘ
モグロビンのλ1およびλ2とλ3における吸光係数の
比である。ζ where kl'/3 e k2'/3 is the ratio of extinction coefficients of deoxygenated hemoglobin at λ1 and λ2 and λ3.
この比は1例えば完全嫌気化されたラット骨格筋吸光光
度変化の比によシ求める事ができる。すなわちラットの
完全嫌気状態下10%02吸入)でヘマトクリット(以
下Hctと略す)の異なる血液を流しながらその都度λ
1.λ2.λ3の波長光を交互に照射して得られる吸光
度をプロットし、 )lctに基づくλl、λ2とλ3
の吸光度の相関グラフを作成する。その直線成分におけ
る吸光度変化の波長間の比を求めることによシ前記係数
比が測定できる。This ratio can be determined by, for example, the ratio of the change in absorbance of a rat skeletal muscle that has been completely anaerobic. In other words, under completely anaerobic conditions in rats (10% 02 inhalation), blood with different hematocrit (hereinafter abbreviated as Hct) was flowing, and λ was adjusted each time.
1. λ2. Plot the absorbance obtained by alternately irradiating light with a wavelength of λ3, and calculate λl, λ2 and λ3 based on )lct.
Create a correlation graph of absorbance. The coefficient ratio can be measured by finding the ratio of absorbance changes in the linear component between wavelengths.
また、 kl/に3. kg/ksに関しても完全好気
状態で同様の実験をすることによシ求める事ができる。Also, kl/3. kg/ks can also be determined by conducting a similar experiment under completely aerobic conditions.
以上の係数は全てin vivoの系でも算出可能であ
る。All of the above coefficients can also be calculated in an in vivo system.
なお、ある状態をnとし、完全好気状態(動静脈血液酸
素飽和度中100)をa、完全嫌気状態(動静脈血液酸
素飽和度中O)をbとすれば(HbOz)n。If a certain state is n, a completely aerobic state (arteriovenous blood oxygen saturation of 100) is a, and a completely anaerobic state (arteriovenous blood oxygen saturation is O) is (HbOz)n.
(Hb)n 、 (IHb:lnは次のように表わされ
る。(Hb)n, (IHb:ln is expressed as follows.
(HbOz)J3=△(HbOz)*−bKi= ((
k;/ks )ΔA1n−’ (kt’/IC5)△A
zn−b)/K”((k2’/に3)lOgI+/It
(kt/)C3)A!ogIz/Izn〕/K(H
b 、lJ<3=△(Hb)vt<<。(HbOz)J3=△(HbOz)*-bKi= ((
k;/ks)ΔA1n-'(kt'/IC5)ΔA
zn-b)/K"((k2'/to3)lOgI+/It
(kt/)C3)A! ogIz/Izn]/K(H
b, lJ<3=Δ(Hb)vt<<.
=(−(kz/ki)△A+n−a+ (k1/に3)
△Az −”)/に−(−(kz/ICs)logII
a/ITo+(k+/に3MogI2シエ2°)/K〔
エト(b)hk3 = (HbOz)nkコ+ (Hb
〕nk3ここで△(HbOz)n−b :状gbからの
酸素化型ヘモグロビン変化量
△(Hb)n−a :状態aがらの脱酸素化型ヘモグロ
ビン変化量
ΔA1”−b:状態すの時の波長λ1の吸光度変化工I
n=状態nの時の波長λlの透過光量従って元の状態か
ら完全好気状態にする事にょシ脱酸素イζ型ヘモグロビ
ンの絶対量が、完全嫌気状態にする、と、とによシ酸素
化型ヘモグロビンの絶対量が求められる。=(-(kz/ki)△A+n-a+ (3 to k1/)
△Az −”)/ni−(−(kz/ICs)logII
a/ITo+(3MogI2she2° to k+/)/K[
et(b)hk3 = (HbOz)nkko+ (Hb
]nk3 where △(HbOz)n-b: Amount of change in oxygenated hemoglobin from state gb △(Hb)na-a: Amount of change in deoxygenated hemoglobin from state a ΔA1''-b: When in state A Absorbance change function I for wavelength λ1
n = amount of transmitted light with wavelength λl in state n Therefore, it is necessary to change from the original state to a completely aerobic state. The absolute amount of converted hemoglobin is determined.
(ホ)実施例
実施例1
第5図にこの発明のヘモグロビン測定法を実施する装置
の一例のブロック、図を示す。この装置はラットを用い
て行なうモデル実験のブロック図である。図において(
1)はフローコ°ントロール、(2)は加湿器、(3)
は人口呼吸装置、(4)は光源、(5)はモノクロメー
タ、(6)は光電子増倍管(PM)、(7)はLOG変
換器、(8)はアナログ/デジタル変換器、(9)ハC
PU 、 ([(lはハイボルテージ(HV)である。(e) Examples Example 1 FIG. 5 shows a block diagram of an example of an apparatus for implementing the hemoglobin measurement method of the present invention. This device is a block diagram of a model experiment conducted using rats. In the figure (
1) is a flow control, (2) is a humidifier, (3)
is an artificial respirator, (4) is a light source, (5) is a monochromator, (6) is a photomultiplier tube (PM), (7) is a LOG converter, (8) is an analog/digital converter, (9) )HaC
PU, ([(l is high voltage (HV).
上記(1)(2) (3)はラットの体内を好気状態か
ら嫌気状B″&でのいずれかの状態に調節するための機
構であシ。The above (1), (2), and (3) are mechanisms for adjusting the rat's body from an aerobic state to an anaerobic state.
従って(3)はラットの気管に接続されるよう構成され
ている。また光源(4)から測定部(A)を介して上記
P M (6)までは光ファイバによる光路(a)が形
成されておシ、上記測定部(4)にはこの光路が中断さ
れて照射端部と受光端部が設定されている。そしてこの
これらの照射端部と受光端部との間に、測定対象の生体
組織を挾んで直接測定できるように構成されている。モ
ノクロメータ(5)は測定部(A)の後に位置している
が、前分光にすることもできる。また通常のモノクロメ
ータを使ってもよいが、干渉フィルタを用いて意図する
波長光のみを選択してこれを交互に照射できるような構
成にしてもよい。(3) is therefore configured to be connected to the rat's trachea. Further, an optical path (a) is formed by an optical fiber from the light source (4) to the above PM (6) via the measuring section (A), and this optical path is interrupted at the above measuring section (4). An irradiation end and a light reception end are set. The body tissue to be measured is sandwiched between the irradiating end portion and the light receiving end portion so that the biological tissue to be measured can be directly measured. Although the monochromator (5) is located after the measurement section (A), it can also be used for front spectroscopy. Although a normal monochromator may be used, an interference filter may be used to select only the intended wavelength light and irradiate it alternately.
上記のごとく構成された装置を用いて得られるラット頭
部透過スペクトルによシ、ヘモグロビン(以下Hbと略
す)の酸素飽和度を測定する場合について説明する。一
般に頭部においては近赤外領域に特徴的な吸収ピークを
もつ生体物質として。A case will be described in which the oxygen saturation of hemoglobin (hereinafter abbreviated as Hb) is measured using a rat head transmission spectrum obtained using the apparatus configured as described above. Generally, in the head, it is a biological material that has a characteristic absorption peak in the near-infrared region.
Hbとチトクロムaa3 (以下cytaa3と略すン
が考えられる。そこでラットを好気状B(95%025
%CO2吸入)にしてその吸収スベク) /L/(イ)
を測定し。Hb and cytochrome aa3 (hereinafter abbreviated as cytaa3) are considered. Therefore, rats were placed in an aerobic state B (95%025
%CO2 inhalation) and its absorption rate) /L/(a)
Measure.
その後嫌気状態(100%N2吸入)にして同じくその
吸収ヌペク)/I/(ロ)を測定し、これらの結果につ
いて、吸収ヌベク)/1/(イ)をベースライン(■)
にとシ、さら娯これと吸収スペクト〃(ロ)との差スベ
ク)/v(■)をそれぞれ第6図(B)に示した。この
結果は、ラットから単離されたHbのみを同様に測定し
た結果(第7図)とは着干異なっている。After that, in an anaerobic state (100% N2 inhalation), the absorption nupek) / I / (b) was measured in the same way, and regarding these results, the absorption nubek) / 1 / (a) was compared to the baseline (■)
The difference between the absorption spectra (subek)/v(■) and the absorption spectra (b) are shown in FIG. 6 (B). This result is quite different from the result of similarly measuring only Hb isolated from rats (Fig. 7).
また次に、ラットにフロロカーボン(人工血液)を潅流
してHbを置換させてHb freeの状態にし。Next, the rats were perfused with fluorocarbon (artificial blood) to replace Hb and become Hb-free.
これについて上記と同様のベースライン(■)および差
スペクトル(■)を測定し第6図(〜に示す結果を得た
。この第6図(Nにおける差ヌベク) /1/ (■)
は、明らかにラット頭部におけるcytaa3の酸化還
元レベルの変動をそのまま示しているものであシ。Regarding this, the same baseline (■) and difference spectrum (■) as above were measured, and the results shown in Figure 6 (~) were obtained.
This clearly shows the fluctuations in the redox level of cytaa3 in the rat head.
従って700〜7801m、においてはcytaaBの
酸化還元レベルの変化に伴うスペクトルの変動は殆ど無
いと考えてよい。Therefore, from 700 to 7801 m, it can be considered that there is almost no change in the spectrum due to changes in the redox level of cytaaB.
以上のことから、この波長域に測定波長を設定すること
によシ得られるデータは、Hbの酸素化−脱酸素化のみ
に依存しているということができる。From the above, it can be said that the data obtained by setting the measurement wavelength in this wavelength range depends only on the oxygenation-deoxygenation of Hb.
従って0%02吸入による完全嫌気状態下のラットでの
測定によシH′bO2濃度の0点を設定し、一方100
%02吸入による完全好気状態下での測定によJ) H
bOz濃度のヌバン点を設定することにょシ。Therefore, the 0 point of H'bO2 concentration was set for the measurement in rats under completely anaerobic conditions with 0% 02 inhalation, while 100%
Measured under fully aerobic conditions by inhalation of %02
It is important to set the Nuban point of bOz concentration.
ヘモグロビンの酸素飽和度に関する定量が可能となる。It becomes possible to quantify the oxygen saturation of hemoglobin.
実施例2
第5図に示した装置を用いてλlに700nm、λ2に
730nm、、λ3に805 nmをと’) * Ra
t大腿骨格筋の透過光測光を行った。Example 2 Using the apparatus shown in Fig. 5, 700 nm for λl, 730 nm for λ2, and 805 nm for λ3') * Ra
Transmitted light photometry of the thigh skeletal muscle was performed.
まず上記2波長を用いたRat頭部潅流実験において完
全好気状態(100%02吸入)および完全嫌気状態(
0%02吸入〕の条件下でHCl15〜50%の範囲に
おける血液を潅流して吸光度変化を測定した結果を第1
図に示す。第1図に示すととく1(atの割合と吸光度
変化との間には、良好な直線性を有することが実証され
た(すなわち、上記範囲内で近似的にランベルト−ペー
ルの人前が成立する)。First, in a Rat head perfusion experiment using the above two wavelengths, a completely aerobic state (100% 02 inhalation) and a completely anaerobic state (
The results of perfusing blood in the range of 15 to 50% HCl under conditions of 0% 02 inhalation] and measuring changes in absorbance are shown in the first
As shown in the figure. As shown in FIG. ).
従って、特定波長: 700nm 、730nm、80
5nmにおいて照射光路(光路長d)中での、酸素化型
ヘモグロビン量変動:△(HbOz) 、脱酸素化型ヘ
モグロビン量変動:△(Hb) 、全ヘモグロビン量変
動:△(IHb)に関して前述の■〜■式、が成立する
。Therefore, specific wavelengths: 700nm, 730nm, 80nm
Regarding the variation in oxygenated hemoglobin amount: △ (HbOz), the variation in deoxygenated hemoglobin amount: △ (Hb), and the variation in total hemoglobin amount: △ (IHb) in the irradiation optical path (optical path length d) at 5 nm, the above-mentioned The formulas ■~■ hold true.
次に■′〜■′式のに、’/に、 、 k2’/に、
(脱酸素化型ヘモグロビンの700 nmおよび73
0 nmと805 nmにおける吸光係数の比)を、完
全嫌気化されたラット骨格筋吸光度変化の比により求め
る。Next, in the formula ■'~■', '/, , k2'/,
(700 nm and 73 nm for deoxygenated hemoglobin
The ratio of extinction coefficients at 0 nm and 805 nm) is determined by the ratio of changes in absorbance of completely anaerobic rat skeletal muscle.
これは、ラットの完全嫌気状態下(0%02吸入)で)
lctの異なる血液を流しながらその都度700nm。This was done in rats under completely anaerobic conditions (0% 02 inhalation).
700 nm each time while flowing blood with different lct.
730nm 、805nmの波長光を交互に照射して得
られる吸光度をプロットし)letに基づ<700nm
。Plot the absorbance obtained by alternately irradiating wavelength light of 730 nm and 805 nm) based on let <700 nm
.
730 nmと805nmの吸光度の相関グラフを作成
し得られるグラフの勾配を測定することLり求める。第
2図(a)に上記相関グラフを示す。このグラフより、
kl′/に3=1.50 k2′/ k3= 1.23
となった。This is determined by creating a correlation graph between absorbance at 730 nm and 805 nm and measuring the slope of the resulting graph. FIG. 2(a) shows the above correlation graph. From this graph,
kl'/3=1.50 k2'/k3= 1.23
It became.
またe kl/ k3 m k2 / k3に関しても
完全好気状態で同様の実験をすることにより求める事が
できる(第2図(b)参照)。このグラフより、kl/
に3=0.80 、 kt / k3= 0.86とな
った。Furthermore, e kl/k3 m k2/k3 can also be determined by conducting a similar experiment under completely aerobic conditions (see Figure 2 (b)). From this graph, kl/
3=0.80, kt/k3=0.86.
従って、■′、■′、■′はそれぞれ次のようになる。Therefore, ■′, ■′, and ■′ are respectively as follows.
△(HbOz) k3= 4.23ΔA?0O−5,1
5ΔA730 −■1△(Hb)ks = 2.92
△A700−2.75ΔA73G −■′△(IH
b〕ks = 1.31△A700−2.41ΔA73
0 −■′また。 Rat大腿部に光を照射し、酸素
化型ヘモグロビン量CHbOz、l ks 、脱酸素化
型ヘモグロビン量()Ib〕ki、全ヘモクロビン量(
IF(b″lkaおよび802が吸入ガスを95%02
5%CO2から0%02まで下げた時にどのような挙動
をするかを示したのが第3図である。△(HbOz) k3= 4.23ΔA? 0O-5,1
5ΔA730 −■1Δ(Hb)ks = 2.92
△A700-2.75ΔA73G -■'△(IH
b]ks = 1.31△A700-2.41△A73
0 -■' again. The rat thigh was irradiated with light, and the amount of oxygenated hemoglobin CHbOz, l ks , the amount of deoxygenated hemoglobin ()Ib]ki, and the amount of total hemoglobin (
IF (b″lka and 802 absorbs 95% of inhaled gas 02
Figure 3 shows how it behaves when the CO2 is lowered from 5% CO2 to 0%02.
我々の算出した光学的パラメータによシ各量はうまくモ
ニタされていることがわかる。It can be seen that each quantity is well monitored by the optical parameters that we have calculated.
第4図はこの発明によシフ 50 nmおよび780n
mの波長ベアを用いてRa1頭部の吸入ガス変動に伴な
う酸素化型ヘモグロビン量変化および脱酸素化型ヘモグ
ロビン量変化をモニタできる事をグラフによシ説明した
ものである。この図によれば酸素吸入から窒素吸入に切
シ替えた時に△(Hbo2〕kiが大幅に減少し、Δ(
Hb) k3 が大幅に増加する様子を示しており、
完全嫌気状態(802中O)を続けた後頚静脈を切断し
た際にHbOzが殆んど減少せず肌のみが大きく減少す
ることはこの時ヘモグロビンは殆んど還元型になってい
る事と合致する。FIG. 4 shows the shift of the present invention.
This graph explains that it is possible to monitor changes in the amount of oxygenated hemoglobin and changes in the amount of deoxygenated hemoglobin due to fluctuations in the intake gas at the Ra1 head using the m wavelength bear. According to this figure, when switching from oxygen inhalation to nitrogen inhalation, △(Hbo2)ki decreases significantly, and Δ(
Hb) shows a significant increase in k3,
The fact that when the jugular vein is severed after being in a completely anaerobic state (O in 802), HbOz hardly decreases and only the skin significantly decreases means that at this time, hemoglobin is mostly in the reduced form. Match.
(へ)効果
本発明によれば、照射光路内の生体組織の酸素化型ヘモ
グロビン量変動、脱酸素化型ヘモグロビン量変動、全ヘ
モグロビン変動(すなわち血液量)および酸素飽和度の
経時変化をモニタすることができる。(f) Effects According to the present invention, changes in the amount of oxygenated hemoglobin, changes in the amount of deoxygenated hemoglobin, changes in total hemoglobin (i.e., blood volume), and changes over time in oxygen saturation in living tissues within the irradiation optical path are monitored. be able to.
第1図は、完全好気状態(a)および完全嫌気状態(′
b)でのRat骨格筋における)(ctと吸光度の関係
図。
第2図は、完全好気状態(a)と完全嫌気状態(b)に
おける波長間の吸光度変化の相関図、第3図は、吸入0
2濃度減少に伴うRat大腿部ヘモグロビン状態変化図
、第4図は、吸入ガス酸素濃度を徐々に下げた時のRa
1頭部における酸素化型ヘモグロビン量と脱酸素化型ヘ
モグロビンの挙動図、第5図は。
本発明の方法を実施する装置図、第6図はラットの頭部
潅流下での透過スペクトルについて、好気状態下の吸収
スペクトルをベースライントシて嫌気状態下の吸収スペ
クトルとの差スペクトルヲ示すグラフ図、第7図はラッ
トの遊離されたヘモグロビンについての第6図相轟図で
ある。
尺tLt骨祢荀’>t=BけりHctt吠先屓の関イ禾
図ン皮−!c rfJq啜先展1タイし旬ネ8iワ図寮
7 図
7oo 3oo 9θ0
痕 ゑ
→Figure 1 shows fully aerobic conditions (a) and fully anaerobic conditions ('
Figure 2 is a diagram showing the relationship between ct and absorbance in Rat skeletal muscle at (b). Figure 2 is a diagram showing the correlation between absorbance changes between wavelengths in fully aerobic conditions (a) and fully anaerobic conditions (b). , inhalation 0
Figure 4 shows the change in the state of Rat femoral hemoglobin as the concentration decreases.
Figure 5 is a behavioral diagram of the amount of oxygenated hemoglobin and deoxygenated hemoglobin in one head. FIG. 6 is a diagram of an apparatus for carrying out the method of the present invention, and shows the transmission spectrum of a rat under head perfusion, and the difference spectrum between the absorption spectrum under aerobic conditions and the absorption spectrum under anaerobic conditions. The graphical diagram, Figure 7, is the Figure 6 phase diagram for rat liberated hemoglobin. Shaku tLt bone 祢荀'>t=B keri Hctt's guan'i kezu n skin-! c rfJq sound exhibition 1 Thailand seasonal news 8i Wazu dormitory 7 Figure 7oo 3oo 9θ0 mark ゑ→
Claims (1)
トル変動がヘモグロビンの酸素化−脱酸素化に伴うスペ
クトル変動に比べ無視し得る実質的にヘモグロビンによ
る吸光度変化のみが生ずる波長領域において異なる特定
の2波長λ_1およびλ_2を選択し、これらの波長光
を生体組織に直接照射して各波長についての吸光度変化
ΔA_1およびΔA_2を測定し、この吸光度変化ΔA
_1およびΔA_2と、予め上記特定波長によって得ら
れた吸光係数; k_1:波長λ_1における酸素化型ヘモグロビンの吸
光係数、 k′_1:波長λ_1における脱酸素化型ヘモグロビン
の吸光係数、 k_2:波長λ_2における酸素化型ヘモグロビンの吸
光係数、 k′_2:波長λ_2における脱酸素化型ヘモグロビン
の吸光係数、 及び酸素化型ヘモグロビンと脱酸素化型ヘモグロビンの
等吸収点(波長λ_3)における吸光係数k_3とに基
づいて、上記照射光路中の酸素化型ヘモグロビン量変動
、脱酸素化型ヘモグロビン量変動および/または全ヘモ
グロビン量変動を測定することを特徴とするヘモグロビ
ン測定法。 2、チトクロムaa3酸化還元状態変化に伴うスペクト
ル変動がヘモグロビンの酸素化−脱酸素化に伴うスペク
トル変動に比べて無視し得る波長領域が700〜780
nmである特許請求の範囲第1項記載のヘモグロビン測
定法。[Scope of Claims] 1. In a wavelength range in which spectral fluctuations associated with changes in the redox state of cytochrome aa3 are negligible compared to spectral fluctuations associated with oxygenation-deoxygenation of hemoglobin, and substantially only absorbance changes due to hemoglobin occur. Select two different specific wavelengths λ_1 and λ_2, directly irradiate living tissue with these wavelengths, measure the absorbance changes ΔA_1 and ΔA_2 for each wavelength, and measure the absorbance changes ΔA_1 and ΔA_2 for each wavelength.
_1 and ΔA_2, and the extinction coefficient obtained in advance at the specific wavelength; k_1: extinction coefficient of oxygenated hemoglobin at wavelength λ_1, k'_1: extinction coefficient of deoxygenated hemoglobin at wavelength λ_1, k_2: extinction coefficient at wavelength λ_2 Extinction coefficient of oxygenated hemoglobin, k'_2: Based on the extinction coefficient of deoxygenated hemoglobin at wavelength λ_2, and the extinction coefficient k_3 at the isosbestic point (wavelength λ_3) of oxygenated hemoglobin and deoxygenated hemoglobin A method for measuring hemoglobin, which comprises measuring fluctuations in the amount of oxygenated hemoglobin, fluctuations in the amount of deoxygenated hemoglobin, and/or fluctuations in the amount of total hemoglobin in the irradiation optical path. 2. The wavelength range is 700 to 780, where the spectral fluctuations associated with changes in the redox state of cytochrome aa3 are negligible compared to the spectral fluctuations associated with oxygenation-deoxygenation of hemoglobin.
The hemoglobin measurement method according to claim 1, wherein the hemoglobin measurement method is nm.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62336197A JPH01174940A (en) | 1987-12-29 | 1987-12-29 | Measurement of hemoglobin |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP62336197A JPH01174940A (en) | 1987-12-29 | 1987-12-29 | Measurement of hemoglobin |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH01174940A true JPH01174940A (en) | 1989-07-11 |
Family
ID=18296644
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP62336197A Pending JPH01174940A (en) | 1987-12-29 | 1987-12-29 | Measurement of hemoglobin |
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JP (1) | JPH01174940A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5517987A (en) * | 1993-06-02 | 1996-05-21 | Hamamatsu Photonics K.K. | Method for measuring internal information in scattering medium and apparatus for the same |
US5529065A (en) * | 1993-06-02 | 1996-06-25 | Hamamatsu Photonics K.K. | Method for measuring scattering medium and apparatus for the same |
JP2003528678A (en) * | 2000-03-31 | 2003-09-30 | 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 | Method and apparatus for localizing anomalous regions in a turbid medium |
CN110710982A (en) * | 2019-10-17 | 2020-01-21 | 京东方科技集团股份有限公司 | Method for acquiring model for detecting hemoglobin concentration and method for detecting hemoglobin concentration |
Citations (3)
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---|---|---|---|---|
JPS56104646A (en) * | 1980-01-25 | 1981-08-20 | Minolta Camera Kk | Optical analyzer for forming ratio of element contained in organism |
JPS6111097A (en) * | 1984-06-27 | 1986-01-18 | 三洋電機株式会社 | Washing machine |
JPS6241639A (en) * | 1985-08-19 | 1987-02-23 | 株式会社 ユニソク | Near infrared living body spectroscopic measuring apparatus |
-
1987
- 1987-12-29 JP JP62336197A patent/JPH01174940A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56104646A (en) * | 1980-01-25 | 1981-08-20 | Minolta Camera Kk | Optical analyzer for forming ratio of element contained in organism |
JPS6111097A (en) * | 1984-06-27 | 1986-01-18 | 三洋電機株式会社 | Washing machine |
JPS6241639A (en) * | 1985-08-19 | 1987-02-23 | 株式会社 ユニソク | Near infrared living body spectroscopic measuring apparatus |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5517987A (en) * | 1993-06-02 | 1996-05-21 | Hamamatsu Photonics K.K. | Method for measuring internal information in scattering medium and apparatus for the same |
US5529065A (en) * | 1993-06-02 | 1996-06-25 | Hamamatsu Photonics K.K. | Method for measuring scattering medium and apparatus for the same |
JP2003528678A (en) * | 2000-03-31 | 2003-09-30 | 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 | Method and apparatus for localizing anomalous regions in a turbid medium |
JP4954418B2 (en) * | 2000-03-31 | 2012-06-13 | 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 | Method and apparatus for locating anomalous regions in turbid media |
CN110710982A (en) * | 2019-10-17 | 2020-01-21 | 京东方科技集团股份有限公司 | Method for acquiring model for detecting hemoglobin concentration and method for detecting hemoglobin concentration |
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Debreczeny et al. | Feasibility assessment of optical noninvasive total hemoglobin measurement | |
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