JP3740527B2 - Method and apparatus for measuring brain activity by near infrared spectroscopy - Google Patents

Method and apparatus for measuring brain activity by near infrared spectroscopy Download PDF

Info

Publication number
JP3740527B2
JP3740527B2 JP2001297839A JP2001297839A JP3740527B2 JP 3740527 B2 JP3740527 B2 JP 3740527B2 JP 2001297839 A JP2001297839 A JP 2001297839A JP 2001297839 A JP2001297839 A JP 2001297839A JP 3740527 B2 JP3740527 B2 JP 3740527B2
Authority
JP
Japan
Prior art keywords
rest
total
hemoglobin
change
brain activity
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.)
Expired - Lifetime
Application number
JP2001297839A
Other languages
Japanese (ja)
Other versions
JP2003093390A (en
Inventor
明敏 精山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
National Institute of Information and Communications Technology
Original Assignee
National Institute of Information and Communications Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National Institute of Information and Communications Technology filed Critical National Institute of Information and Communications Technology
Priority to JP2001297839A priority Critical patent/JP3740527B2/en
Publication of JP2003093390A publication Critical patent/JP2003093390A/en
Application granted granted Critical
Publication of JP3740527B2 publication Critical patent/JP3740527B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Landscapes

  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Description

【0001】
【発明の属する技術分野】
本発明は、磁気共鳴撮像装置(以下、MRI)を用いた脳活動計測(以下、fMRI(functional MRI))及び、近赤外線等の光を用いた脳活動活動手段に関する。
【0002】
【従来の技術】
ヒト生体機能の非侵襲計測には、生体の電気的活動を計測する方法(MEG,EEG)と血行動態を計測する方法(fMRI、NIRS)がある。fMRIの目的は、高い空間分解能を有する特徴を持ち、活性化領域を抽出して脳の機能分布を把握すること、及び活性化領域での信号変化率を観察することである。この信号変化率の測定から、特定の刺激に対する脳活動の解明等の研究目的に使用することができる。特に、脳活動計測においては活動部位の同定の常用手段として使用されている。
【0003】
fMRIでの信号変化の原理は、循環血液中の脱酸素ヘモグロビン量の変化に基づく磁性の変化により、生体中の自由水の可動プロトンの実効横緩和時間(T2*)の変化することを利用している。例えば、ヘモグロビンの鉄原子に酸素が結合すると、酸素化ヘモグロビン(動脈血に相当する)となり磁性が消失し、生体中の自由水の可動プロトンの実効横緩和時間(T2*)が大きくなる。fMRIで計測されるパラメーター(△S/S)restは、このT2*の変化を反映している。MRIで実効横緩和とよばれるT2緩和は、横磁化成分が減衰していく過程を示す時定数であり、理想的な均一磁場で得られる信号を意味する。しかし実際は磁場の不均一性があるために信号はT2よりも速く減衰するため、この実際の信号をT2*(ティーツースター)とあらわしてT2とは区別している。fMRIはT2*の信号変化を捉えるものである。
【0004】
仮に、視覚や音響等などにより脳を刺激すると、大脳皮質の神経細胞が興奮し、酸素を消費する。これにより、局所的に脱酸素ヘモグロビン量が増加する。次いで、活性化領域では酸素消費量が増加しているので、動脈血の流入による血流及び血液量が増加する。すなわち、活性化領域中では、酸化ヘモグロビンの増加による磁気的性質の変化と血流及び血液量の変化とが同時に発生し、これらはfMRIの信号に影響する。
このように、T2*は、血流・血液量・血液の酸素化状態のパラメーターが相互に依存し合った結果として得られるものであり、fMRIの解釈が複雑となり、混乱を生じていた。しかし、本来要求されている生理的情報は、これらの要因をそれぞれ分離した血流・血液量・血液の酸素化状態のパラメーターであるが、fMRIのみではその分離が不可能である。
【0005】
このような事項に対して、従来は、計算モデルに必要な血液量や血液の酸素化状態は実測値ではなく、文献値をもとにある仮定値を代入し定性的な推移を予想していた。従って、このようなfMRIの信号推定モデルが提唱されているのみで、情報源が細動脈領域又は、毛細血管領域であるかを同定したり、また、fMRIの信号変化から、血流、血液量、血液の酸素化状態のパラメーターを分離して評価することができなかった。
【0006】
一方で、近赤外光を用いた脳活動計測(近赤外分光法(NIRS))では、脳組織の光吸収特性の変化がもたらす情報を得ることができる。近赤外線は、赤外線(約700〜3000nm)の中でも、可視光領域(約400〜700nm)に最も近い波長領域のことを指す。波長800nm前後の近赤外線は高い生体透過性を持ち、近赤外領域の光(700〜1500nm)は高い生体透過性を持ち、頭皮上から投光した光は脳組織を通過し、生体組織が反射体となり頭皮上からの受光が可能である。近赤外分光法は、この領域において血液中のヘモグロビンが特徴的な吸収バンドを持つことを利用して、生体組織中の血液の酸素化ヘモグロビン(oxy-Hb)、脱酸素化ヘモグロビン(deoxy-Hb)及び全ヘモグロビン([total-Hb])の変化を連続的に検出できる特徴を有する。また、局所脳血液量(rCBV)の変化を扱える計測法として確立されている。
【0007】
【発明が解決しようとする課題】
そこで、本発明では、MRIで得られた信号と近赤外線を用いた脳機能解析から、fMRI信号である(△S/S)restを求めること、並びに、当該信号が細静脈や毛細血管等の如何なる部位の信号かを判断する手段を提供することに寄与する手段を提供することを課題とする。
【0008】
【課題を解決するための手段】
上記の課題を解決するために、本発明の脳活動計測装置は、近赤外線を用いた脳活動計測装置において、付属するコンピューターが、少なくとも入力されたMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対するヘモグロビン変化量([△Hb])、血液酸素化率の変化分([△Y])を少なくとも記録する記録手段、これらの数値を次の数式に適用して、△S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)該計算結果より機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出する演算手段を有することを特徴とする。
同様に、本発明の脳活動計測方法は、近赤外線を用いた脳活動計測装置において、付属するコンピューターで、少なくとも入力されたMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対するヘモグロビン変化量([△Hb])、血液酸素化率の変化分([△Y])を少なくとも記録し、これらの数値を次のいずれかの数式に適用して、△S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}または、△S/Srest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)該計算結果より機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出することを特徴とする。
また、本発明のコンピューターソフトウエアは、近赤外線を用いた脳活動計測装置に付属するコンピューターにおいて、少なくとも入力されたMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対するヘモグロビン変化量([△Hb])、血液酸素化率の変化分([△Y])を少なくとも記録する記録部と、これらの数値を次のいずれかの数式に適用して、S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}または、△S/Srest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)該計算結果より機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出する演算部を有することを特徴とする
【0009】
前記数式部分が、(△S/S)rest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}の場合は、fMRI信号が細静脈を反映している時に使用され、又は当該式に当てはまる時は細静脈を反映している。これらの意味・定義は以下で同じである。
前記数式部分が、(△S/S)rest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}の場合は、特定の刺激に対して脳の毛細血管のヘモグロビンが変化する場合に用いることができる。
【0010】
上記本発明により、MRIの構造画像及び近赤外線を用いた計測法から、従来はfMRIでしか得られないfMRI信号(△S/S)restを自動的に算出することができる。
また、得られたfMRI信号が如何なる成分であるかを定めることができる。すなわち、fMRI信号は全ヘモグロビン量、酸化ヘモグロビン量等が反映され、また、細静脈若しくは毛細血管のいずれかの部位を反映するか定めることができる。
【0011】
さらに、fMRI及び近赤外線を用いて並行して脳活動の計測を行ない、該fMRI測定による信号強度を経時的に表示するfMRI信号強度表示手段、該近赤外線測定による細静脈でのヘモグロビンの変化を表示する近赤外線細静脈ヘモグロビン変化表示手段、該近赤外線測定による毛細静脈血管でのヘモグロビンの変化を表示する近赤外線毛細静脈血管ヘモグロビン変化表示手段とを有する装置で構成してもよい。すると、その表示により、fMRI信号と近赤外線で得られた信号を同画面で表示等することにより、fMRI信号が近赤外線で得られた信号のいずれに帰属するか判断することができる。上記の細静脈若しくは毛細静脈血管でのヘモグロビンの変化は上記式により算出させて行う。
【0012】
また、脳活動計測においては、チェッカーボードの反転による視覚刺激を与えて、少なくともfMRI((△S/S)rest)信号、酸素化ヘモグロビン、脱酸素化ヘモグロビン及び全ヘモグロビン量のいずれかを測定するようにしてもよい。チェッカーボードの反転による視覚刺激は0.5Hz又は14Hzの視覚刺激とすることで、fMRI及び近赤外線での測定脳後頭部の生体情報の変化が大きくなり、測定に適している。
【0013】
【発明の実施の形態】
本発明では、fMRIの信号変化が脳循環・代謝の変化に伴うヘモグロビンの磁性変化を反映しているのに対して、近赤外光を用いた脳活動計測(近赤外分光法(NIRS))では、脳組織の光散乱特性の変化がもたらす情報を得ることができる。近赤外線は、赤外線(約700〜3000nm)の中でも、可視光領域(約400〜700nm)に最も近い波長領域のことを指す。波長800nm前後の近赤外線は高い生体透過性を持ち、頭皮上から投光した近赤外線は脳組織を通過し、さらに頭皮上からの受光が可能である。近赤外分光法は、この領域において血液中のヘモグロビンが特徴的な吸収バンドを持つことを利用して、生体組織中の血液の酸素化ヘモグロビン(oxy-Hb)、脱酸素化ヘモグロビン(deoxy-Hb)及び全ヘモグロビン([total-Hb])の変化を連続的に検出できる特徴を有する。また、局所脳血液量(rCBV)の変化を扱える計測法として確立されている。
そこで、本発明ではfMRIの測定と並行して、NIRSの測定を行い、赤外分光法によるfMRIの信号変化を帰属する手段を提供する。
【0014】
【実施例】
実験条件として、ヒト視覚野賦活時におけるfMRIにより得られた血行動態の変化を、本発明の方法により、NIRSにより得られる結果で補足できることを、実施例として示した。被験者は健常成人男性を6名(24歳〜43歳)を対象にfMRIの測定と平行して、NIRSの測定を行う。視覚刺激はコンピューターのモニター上に写し出されるチェッカーボード(刺激周波数:0.5,1.4,4.7及び14Hzで点滅させる)を用いた。実験では4種類の刺激周波数を擬似ランダムに計16回提示した(測定時間は約16分間)(図1)。
図1の上段は、視覚刺激の休止状態と刺激状態のモニター表示を示したものである。図1の下段は、実験の条件を示したものであり、ランダムに視覚刺激の強度が変化していることが示される。また、視覚刺激のヘルツ(Hz)は、チェッカーボードの反転の速さから定めたものである。
【0015】
近赤外分光法による脳活動測定は、CW型近赤外分光装置を用いた。測定部位は、視覚野を含む後頭部(7cm×7cmの領域)を近赤外マッピング装置(OPTIM-A、柳田結集型特別グループ、通信総合研究所、1999)を用いて、ヘモグロビンパラメーターの測定を行った。測定チャンネルは、4×4の16チャンネルであり(図2)、測定波長は、776nm、804nm、828nmと400msの間隔で順次測定した。ヘモグロビンパラメーターは、以下の式1で表せるModified Beer-Lambert法により算出した。
この測定方法・計算方法により、△oxy-Hb(酸素化ヘモグロビン変化量)、△deoxy-Hb(脱酸素化ヘモグロビン変化量)、△total Hb(全ヘモグロビン変化量)を算出することができる。
【式1】

Figure 0003740527
【0016】
一方、fMRIによる脳活動の計測と解析については、(1)装置は、Siemens VISION(Germany),1.5T System、(2)撮像法は、GER-EPI法、(3)撮像パラメーターは、TR 3.9sec,TE 55.24msec, FA 90 degree、(4)スライスは、Axialスライス 32(厚さmm/1枚、間隔 0mm)、(5)ピクセルサイズ 4mm×4mm×4mm (Fov 256mm×256mm Matrix 64×64)である。解析は、(6)Motion CorrectionはAIR3.0、(7)AVS/Express、(8)構造画像と機能画像の重ね合わせは、Analyze PC2.5(Mayo Fundation)及びSPM99を使用した。
【0017】
測定は、MRI装置の被験者の頭部を乗せる部分に、近赤外分光法で測定することができるように近赤外マッピング装置のプローブを置いた。ここで、本発明による方法は、fMRIの測定と同時でもよく、また、同条件下でfMRIの測定の前後でNIRSの測定を行ってもよい。NIRSの測定は、CW型近赤外分光装置、時間分解型近赤外分光装置、又は周波数領域を使った強度変調型を用いることが挙げられる。
【0018】
測定結果は、NIRSの測定とfMRIの測定で、上述の条件による実験では、活動部位の検出については両測定とも、同じ領域が活動されていることが示された。次に、NIRSの測定では、視覚刺激に伴う後頭部ヘモグロビンの変化は、図3のグラフに示したように、0.5Hz及び14Hzの刺激で全ヘモグロビン量及び酸素化ヘモグロビン量の増加が大きいことが示された。
【0019】
一方、fMRIの測定では、図4に示すように1.4Hz及び4.7Hzで大きな信号強度が見られた。グラフ横軸は時間(秒)を表し、縦軸は当該活動部位の信号強度を表している。Correlation Coefficient(相関係数)はボックススカーフィッチングで、信号変化がタスク負荷にどれだけマッチしているのか相関を出したものであり、rが0.75以上であれば、相関が有ると示される。
【0020】
また、図4では、fMRI信号と近赤外線を用いた測定(NIRS)の結果を同画面で表示したものである。ヘモグロビンパラメーターの測定は上述のように、776nm、804nm、828nmと400msの間隔で順次測定した。ヘモグロビンパラメーターは、前記のModified Beer-Lambert法により算出した。上記式である(△S/S)rest= (TE・R2*rest)・{2△Y/(1―Yrest) ― △[total-Hb]/[total-Hb]rest}(第1式)若しくは、(△S/S)rest= (TE・R2*rest)・{△Y/(1―Yrest) ― △[total-Hb]/[total-Hb]rest}(第2式)に、これらヘモグロビンパラメーター等を代入して計算した。絶対値のヘモグロビン量は、時間分解型近赤外分光装置を用いることが適している。第1式は、細静脈での信号が反映される場合、第2式は、毛細血管での信号が反映される場合である。図4のfMRI信号はそのままのデータを表示し、細静脈と毛細血管の信号は、個々のヘモグロビンパラメーターを上記式に従って代入して算出されたグラフである。結果は2人の実験で同様の結果が得られ、本実施例では、fMRI信号は細静脈の信号が反映されていること、近赤外線の測定からfMRI信号を算出できたことが示された。
【0021】
【発明の効果】
本発明により、MRIの構造画像のデータ及び近赤外線の測定結果より、fMRIの測定でしか得られないfMRI信号強度((△S/S)rest)を算出することができる。また、fMRI信号強度((△S/S)rest)及び近赤外線の測定結果より、その信号の帰属部位が細静脈又は毛細血管であるかを判断することができる。
【図面の簡単な説明】
【図1】被験者に視覚刺激を与える手順を示す説明図
【図2】近赤外線を生体に照射及び受光するファイバー先端部を示す説明図
【図3】各視覚刺激におけるfMRI信号強度を示したグラフ
【図4】甲及び乙のfMRI及び近赤外線測定から算出したfMRI信号(細静脈・毛細血管)を経時的に示したグラフ[0001]
BACKGROUND OF THE INVENTION
The present invention relates to brain activity measurement (hereinafter referred to as fMRI (functional MRI)) using a magnetic resonance imaging apparatus (hereinafter referred to as MRI) and brain activity activity means using light such as near infrared rays.
[0002]
[Prior art]
Non-invasive measurement of human biological functions includes a method for measuring electrical activity (MEG, EEG) and a method for measuring hemodynamics (fMRI, NIRS). The purpose of fMRI is to have a feature with high spatial resolution, to extract the activation region and grasp the functional distribution of the brain, and to observe the signal change rate in the activation region. From the measurement of this signal change rate, it can be used for research purposes such as elucidation of brain activity for a specific stimulus. In particular, in brain activity measurement, it is used as a routine means for identifying active sites.
[0003]
The principle of signal change in fMRI is based on the fact that the effective transverse relaxation time (T2 * ) of mobile protons in free water in the living body changes due to the change in magnetism based on the change in the amount of deoxygenated hemoglobin in the circulating blood. ing. For example, when oxygen binds to the iron atom of hemoglobin, it becomes oxygenated hemoglobin (corresponding to arterial blood), the magnetism disappears, and the effective lateral relaxation time (T2 * ) of mobile protons in free water in the living body increases. The parameter (ΔS / S) rest measured by fMRI reflects this change in T2 * . T2 relaxation called effective transverse relaxation in MRI is a time constant indicating a process in which the transverse magnetization component is attenuated, and means a signal obtained with an ideal uniform magnetic field. However, since the signal is actually attenuated faster than T2 due to the inhomogeneity of the magnetic field, this actual signal is expressed as T2 * (tea to star) and is distinguished from T2. fMRI captures signal changes in T2 * .
[0004]
If the brain is stimulated by vision, sound or the like, neurons in the cerebral cortex are excited and consume oxygen. Thereby, the amount of deoxygenated hemoglobin locally increases. Next, since the oxygen consumption is increased in the activated region, the blood flow and blood volume due to the inflow of arterial blood increase. That is, in the activated region, a change in magnetic properties due to an increase in oxyhemoglobin and a change in blood flow and blood volume occur simultaneously, which affect the fMRI signal.
Thus, T2 * is obtained as a result of mutually dependent parameters of blood flow, blood volume, and blood oxygenation state, which complicates interpretation of fMRI and causes confusion. However, the physiological information originally required is parameters of blood flow, blood volume, and blood oxygenation state from which these factors are separated, but the separation is impossible only by fMRI.
[0005]
In the past, qualitative transitions were predicted by substituting hypothetical values based on literature values for blood volume and blood oxygenation required for calculation models instead of actual measurement values. It was. Therefore, only such an fMRI signal estimation model has been proposed, and it is identified whether the information source is an arteriole region or a capillary region, and the blood flow and blood volume are determined from the fMRI signal change. The parameters of blood oxygenation status could not be separated and evaluated.
[0006]
On the other hand, in brain activity measurement using near-infrared light (near-infrared spectroscopy (NIRS)), information resulting from a change in light absorption characteristics of brain tissue can be obtained. Near-infrared rays refer to the wavelength region closest to the visible light region (about 400 to 700 nm) among infrared rays (about 700 to 3000 nm). Near-infrared light with a wavelength of around 800 nm has high biological permeability, light in the near-infrared region (700-1500 nm) has high biological permeability, and the light projected from the scalp passes through brain tissue, It becomes a reflector and can receive light from the scalp. Near-infrared spectroscopy uses the characteristic absorption band of hemoglobin in blood in this region, so that oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin (deoxy-Hb) It has the feature that changes in Hb) and total hemoglobin ([total-Hb]) can be detected continuously. It has also been established as a measurement method that can handle changes in local cerebral blood volume (rCBV).
[0007]
[Problems to be solved by the invention]
Therefore, in the present invention, the (M / S) rest, which is an fMRI signal, is obtained from a brain function analysis using a signal obtained by MRI and near-infrared light, and the signal is obtained from venules, capillaries, etc. It is an object of the present invention to provide a means that contributes to providing a means for determining what kind of part the signal is.
[0008]
[Means for Solving the Problems]
In order to solve the above-described problems, a brain activity measuring apparatus according to the present invention is a brain activity measuring apparatus using near infrared rays, in which an attached computer has at least an echo time (TE) and a resting time when MRI is input. Recorded the effective lateral relaxation time (T2 * rest), total hemoglobin measured by the brain activity measuring device ([total-Hb]), hemoglobin change at rest ([△ Hb]), blood oxygenation rate Means for recording at least the amount of change ([ΔY]), and applying these numerical values to the following equation, ΔS / Srest = (TE · T2 * rest) · {2ΔY / (1−Yrest ) ― △ [total-Hb] / [total-Hb] rest} (However, “rest” means “resting (resting)”, and [total-Hb] rest is “all resting” “Hemoglobin amount” and “Yrest” indicate the oxygenation rate of hemoglobin at rest) Δ is a functional MRI (fMRI) signal from the calculation result / Characterized by having a calculating means for calculating Srest the (variation ratio of from resting against MRI signal intensity at rest).
Similarly, the brain activity measuring method of the present invention is a brain activity measuring device using near infrared rays, and at least an input echo time (TE) at the time of MRI measurement and an effective lateral relaxation time at rest ( T2 * rest) is recorded, and the total hemoglobin measured by the brain activity measuring device ([total-Hb]), the amount of hemoglobin change at rest ([△ Hb]), and the change in blood oxygenation rate ([△ Y]) at least, and apply these numbers to one of the following formulas: △ S / Srest = (TE ・ T2 * rest) ・ {2 △ Y / (1-Yrest) ― △ [total -Hb] / [total-Hb] rest} or △ S / Srest = (TE ・ T2 * rest) ・ {△ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest} (However, “rest” means “resting state (resting)”, [total-Hb] rest is “total hemoglobin amount at resting”, and “Yrest” is oxygenation of resting hemoglobin. ΔS / Srest (ratio of change from rest to MRI signal intensity at rest), which is a functional MRI (fMRI) signal, is calculated from the calculation result.
In addition, the computer software of the present invention is a computer attached to a brain activity measuring apparatus using near infrared rays, and at least the input echo time (TE) at the time of MRI measurement and effective lateral relaxation time at rest (T2 * rest ) As well as the total hemoglobin measured by the brain activity measuring device ([total-Hb]), the amount of hemoglobin change at rest ([△ Hb]), and the change in blood oxygenation rate ([△ Y]) Apply at least one of the following formulas to the recording unit that records at least S / Srest = (TE · T2 * rest) · {2ΔY / (1−Yrest) —Δ [total- Hb] / [total-Hb] rest} or ΔS / Srest = (TE · T2 * rest) · {ΔY / (1-Yrest)-△ [total-Hb] / [total-Hb] rest} ( However, “rest” means “resting (resting)”, [total-Hb] rest is “total hemoglobin amount at rest”, and “Yrest” is resting hemoglobin. It has a calculation unit for calculating ΔS / Srest (ratio of change from rest to MRI signal intensity at rest) which is a functional MRI (fMRI) signal from the calculation result (indicating the oxygenation rate of globin) [0009]
When the formula part is (ΔS / S) rest = (TE · T2 * rest) · {2ΔY / (1-Yrest) -Δ [total-Hb] / [total-Hb] rest} Used when the fMRI signal reflects venules, or reflects venules when the formula is true. These meanings and definitions are the same below.
Specific when the mathematical part is (ΔS / S) rest = (TE · T2 * rest) · {ΔY / (1-Yrest) -Δ [total-Hb] / [total-Hb] rest} It can be used when the hemoglobin in the capillaries of the brain changes in response to the stimulation.
[0010]
According to the present invention, an fMRI signal (ΔS / S) rest that has been conventionally obtained only by fMRI can be automatically calculated from an MRI structure image and a measurement method using near infrared rays.
It is also possible to determine what component the obtained fMRI signal is. That is, the fMRI signal reflects the total hemoglobin amount, the oxidized hemoglobin amount, and the like, and can determine whether to reflect any part of the venule or capillary.
[0011]
Furthermore, fMRI and near infrared rays are used to measure brain activity in parallel, fMRI signal intensity display means for displaying the signal intensity obtained by the fMRI measurement over time, and changes in hemoglobin in the venule caused by the near infrared measurement. You may comprise with the apparatus which has a near-infrared venule hemoglobin change display means to display, and a near-infrared capillary venous hemoglobin change display means to display the change of hemoglobin in the capillary vein by the near-infrared measurement. Then, by displaying the fMRI signal and the signal obtained with the near infrared ray on the same screen, it is possible to determine to which of the signals obtained with the near infrared ray the fMRI signal belongs. The change in hemoglobin in the venule or capillary vein is calculated by the above formula.
[0012]
In brain activity measurement, a visual stimulus is applied by reversing the checkerboard, and at least one of the fMRI ((ΔS / S) rest) signal, oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin is measured. You may do it. The visual stimulus by reversing the checkerboard is a visual stimulus of 0.5 Hz or 14 Hz, and the change in the biological information of the measurement brain occipital region at fMRI and near infrared is large, which is suitable for measurement.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
In the present invention, the signal change of fMRI reflects the magnetic change of hemoglobin accompanying the change of cerebral circulation and metabolism, whereas the brain activity measurement using near infrared light (near infrared spectroscopy (NIRS)). ) Provides information resulting from changes in the light scattering characteristics of brain tissue. Near-infrared rays refer to the wavelength region closest to the visible light region (about 400 to 700 nm) among infrared rays (about 700 to 3000 nm). Near-infrared rays with a wavelength of around 800 nm have high biological permeability, and the near-infrared rays projected from the scalp pass through brain tissue and can be received from the scalp. Near-infrared spectroscopy uses the characteristic absorption band of hemoglobin in blood in this region, so that oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin (deoxy-Hb) It has the feature that changes in Hb) and total hemoglobin ([total-Hb]) can be detected continuously. It has also been established as a measurement method that can handle changes in local cerebral blood volume (rCBV).
Therefore, in the present invention, NIRS measurement is performed in parallel with fMRI measurement, and means for assigning fMRI signal change by infrared spectroscopy is provided.
[0014]
【Example】
As an experimental condition, it was shown as an example that the change in hemodynamics obtained by fMRI during activation of the human visual cortex can be supplemented with the results obtained by NIRS by the method of the present invention. The subjects measure NIRS in parallel with the fMRI measurement for 6 healthy adult males (24 to 43 years old). For visual stimulation, a checker board (stimulation frequencies: blinking at 0.5, 1.4, 4.7 and 14 Hz) projected on a computer monitor was used. In the experiment, four types of stimulation frequencies were presented pseudo-randomly 16 times in total (measurement time was about 16 minutes) (FIG. 1).
The upper part of FIG. 1 shows the monitor display of the resting state and the stimulating state of the visual stimulus. The lower part of FIG. 1 shows the experimental conditions and shows that the intensity of the visual stimulus changes randomly. The visual stimulation hertz (Hz) is determined from the reversal speed of the checkerboard.
[0015]
The brain activity measurement by near infrared spectroscopy was performed using a CW type near infrared spectrometer. Measure the hemoglobin parameter using the near-infrared mapping device (OPTIM-A, Yu Yanagida Special Group, Communications Research Laboratory, 1999) for the back of the head (7 cm x 7 cm area) including the visual cortex. It was. The measurement channels were 4 × 4 16 channels (FIG. 2), and the measurement wavelengths were sequentially measured at intervals of 776 nm, 804 nm, 828 nm and 400 ms. The hemoglobin parameter was calculated by the Modified Beer-Lambert method expressed by the following formula 1.
By this measurement method / calculation method, Δoxy-Hb (oxygenated hemoglobin change amount), Δdeoxy-Hb (deoxygenated hemoglobin change amount), and Δtotal Hb (total hemoglobin change amount) can be calculated.
[Formula 1]
Figure 0003740527
[0016]
On the other hand, regarding the measurement and analysis of brain activity by fMRI, (1) the device is Siemens VISION (Germany), 1.5T System, (2) the imaging method is the GER-EPI method, and (3) the imaging parameter is TR 3.9. sec, TE 55.24msec, FA 90 degree, (4) slice is Axial slice 32 (thickness mm / 1 sheet, interval 0mm), (5) pixel size 4mm × 4mm × 4mm (Fov 256mm × 256mm Matrix 64 × 64 ). For analysis, (6) Motion Correction used AIR3.0, (7) AVS / Express, and (8) Structured image and functional image were superimposed using Analyze PC2.5 (Mayo Fundation) and SPM99.
[0017]
In the measurement, the probe of the near-infrared mapping apparatus was placed on the portion of the MRI apparatus where the subject's head is placed so that the measurement can be performed by near-infrared spectroscopy. Here, the method according to the present invention may be performed simultaneously with the fMRI measurement, or the NIRS measurement may be performed before and after the fMRI measurement under the same conditions. NIRS can be measured by using a CW type near-infrared spectrometer, a time-resolved near-infrared spectrometer, or an intensity modulation type using a frequency domain.
[0018]
The measurement results were NIRS measurement and fMRI measurement. In the experiment under the above-mentioned conditions, it was shown that the same region was activated for both of the measurements for the detection of the active site. Next, NIRS measurement shows that the changes in occipital hemoglobin associated with visual stimulation show a large increase in total hemoglobin and oxygenated hemoglobin levels at 0.5 Hz and 14 Hz stimulation, as shown in the graph of FIG. It was done.
[0019]
On the other hand, in the fMRI measurement, as shown in FIG. 4, large signal intensities were observed at 1.4 Hz and 4.7 Hz. The horizontal axis of the graph represents time (seconds), and the vertical axis represents the signal intensity of the active site. Correlation Coefficient (correlation coefficient) is box scarf switching, and indicates how much the signal change matches the task load. If r is 0.75 or more, it indicates that there is a correlation.
[0020]
In FIG. 4, the result of measurement (NIRS) using the fMRI signal and near infrared rays is displayed on the same screen. As described above, hemoglobin parameters were measured sequentially at intervals of 776 nm, 804 nm, 828 nm and 400 ms. The hemoglobin parameter was calculated by the modified Beer-Lambert method. (ΔS / S) rest = (TE · R2 * rest) · {2ΔY / (1−Yrest) −Δ [total-Hb] / [total-Hb] rest} (the first equation) Or (△ S / S) rest = (TE ・ R2 * rest) ・ {△ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest} (Equation 2) It was calculated by substituting hemoglobin parameters. For the absolute amount of hemoglobin, it is suitable to use a time-resolved near-infrared spectrometer. The first expression is a case where a signal in a venule is reflected, and the second expression is a case where a signal in a capillary is reflected. The fMRI signal of FIG. 4 displays the data as it is, and the venule and capillary signal are graphs calculated by substituting individual hemoglobin parameters according to the above formula. As a result, similar results were obtained in two experiments. In this example, it was shown that the fMRI signal reflected the venule signal, and that the fMRI signal could be calculated from the near infrared measurement.
[0021]
【The invention's effect】
According to the present invention, the fMRI signal intensity ((ΔS / S) rest) that can be obtained only by the fMRI measurement can be calculated from the MRI structural image data and the near-infrared measurement result. Further, from the measurement result of the fMRI signal intensity ((ΔS / S) rest) and the near-infrared ray, it can be determined whether the part to which the signal belongs is a venule or a capillary.
[Brief description of the drawings]
FIG. 1 is an explanatory diagram showing a procedure for giving a visual stimulus to a subject. FIG. 2 is an explanatory diagram showing a fiber tip that irradiates and receives a near infrared ray on a living body. FIG. 3 is a graph showing fMRI signal intensity in each visual stimulus. FIG. 4 is a graph showing fMRI signals (fine veins / capillaries) calculated from fMRI and near-infrared measurements of A and B over time.

Claims (6)

近赤外線を用いた脳活動計測装置において、
付属するコンピューターが、少なくとも入力されたMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、
脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対する全ヘモグロビン量の変化量 ( [total-Hb])、血液酸素化率の変化分(△Y)を少なくとも記録する記録手段、
これらの数値を次の数式に適用して、
△S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)
該計算結果より機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出する演算手段を有する
ことを特徴とする脳活動計測装置。
In the brain activity measuring device using near infrared rays,
The attached computer records at least the input echo time (TE) at the time of MRI measurement and the effective transverse relaxation time (T2 * rest) at rest,
Record at least the amount of total hemoglobin ([total-Hb]) measured by the brain activity measuring device, the amount of change in total hemoglobin relative to rest ( [total-Hb]) , and the change in blood oxygenation rate (△ Y) Recording means,
Apply these numbers to the following formula:
△ S / Srest = (TE ・ T2 * rest) ・ {2 △ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
(However, “rest” means “resting (resting)”, [total-Hb] rest is “total amount of hemoglobin at rest”, and “Yrest” is the oxygenation rate of resting hemoglobin. Indicate)
A brain activity measuring device comprising a computing means for calculating ΔS / Srest (ratio of change from rest to MRI signal intensity at rest) which is a functional MRI (fMRI) signal from the calculation result .
近赤外線を用いた脳活動計測装置において、
付属するコンピューターが、少なくとも入力されたMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、
脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対する全ヘモグロビン量の変化量(△ [total-Hb])、血液酸素化率の変化分(△Y)を少なくとも記録する記録手段、
これらの数値を次の数式に適用して、
△S/Srest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)
該計算結果より機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出する演算手段を有する
ことを特徴とする脳活動計測装置。
In the brain activity measuring device using near infrared rays,
The attached computer records at least the input echo time (TE) at the time of MRI measurement and the effective transverse relaxation time (T2 * rest) at rest,
Record at least the amount of total hemoglobin ([total-Hb]) measured by the brain activity measuring device, the amount of change in total hemoglobin relative to rest (△ [total-Hb]) , and the change in blood oxygenation rate (△ Y) Recording means,
Apply these numbers to the following formula:
△ S / Srest = (TE ・ T2 * rest) ・ {△ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
(However, “rest” means “resting (resting)”, [total-Hb] rest is “total amount of hemoglobin at rest”, and “Yrest” is the oxygenation rate of resting hemoglobin. Indicate)
A brain activity measuring device comprising a computing means for calculating ΔS / Srest (ratio of change from rest to MRI signal intensity at rest) which is a functional MRI (fMRI) signal from the calculation result .
近赤外線を用いた脳活動計測装置において、
付属するコンピューターによって、少なくともMRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、
脳活動計測装置が測定した全ヘモグロビン量([total-Hb])、安静時に対する全ヘモグロビン量の変化量 ( [total-Hb])、血液酸素化率の変化分(△Y)を少なくとも記録し、
これらの数値を次のいずれかの数式:
△S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
または、
△S/Srest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)
に適用した計算結果より、機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を算出する
ことを特徴とする脳活動計測方法。
In the brain activity measuring device using near infrared rays,
With the attached computer, record at least the echo time (TE) at the time of MRI measurement and the effective transverse relaxation time (T2 * rest) at rest,
Record at least the amount of total hemoglobin ([total-Hb]) measured by the brain activity measuring device, the amount of change in total hemoglobin relative to rest ( [total-Hb]) , and the change in blood oxygenation rate (△ Y) And
These numbers can be any of the following formulas:
△ S / Srest = (TE ・ T2 * rest) ・ {2 △ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
Or
△ S / Srest = (TE ・ T2 * rest) ・ {△ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
(However, “rest” means “resting (resting)”, [total-Hb] rest is “total amount of hemoglobin at rest”, and “Yrest” is the oxygenation rate of resting hemoglobin. Indicate)
A method of measuring brain activity, comprising calculating ΔS / Srest (ratio of change from rest to MRI signal intensity at rest), which is a functional MRI (fMRI) signal, from the calculation result applied to.
近赤外線を用いた脳活動計測装置に付属するコンピューターにおけるソフトウェアにおいて、
MRI測定時のエコー時間(TE)及び安静時の実効横緩和時間(T2*rest)を記録すると共に、
脳活動計測装置によって測定され入力された全ヘモグロビン量([total-Hb])、安静時に対する全ヘモグロビン量の変化量 ( [total-Hb])、血液酸素化率の変化分(△Y)を少なくとも記録部に記録する記録ステップと、
これらの数値を次のいずれかの数式:
△S/Srest= (TE・T2*rest)・{2△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
または、
△S/Srest= (TE・T2*rest)・{△Y/(1―Yrest) ―△[total-Hb]/[total-Hb]rest}
(ただし、「rest」の表示は「休止状態(安静時)」の意味であり、[total-Hb]restは「安静時の全ヘモグロビン量」、「Yrest」は安静時のヘモグロビンの酸素化率を示す)
に適用して演算部で計算を行ない、機能的MRI(fMRI)信号である△S/Srest (安静時のMRI信号強度に対する安静時からの変化分の比)を演算部で算出する演算ステップを有する
ことを特徴とするコンピューターソフトウエア。
In the software on the computer attached to the brain activity measuring device using near infrared rays,
Record the echo time (TE) during MRI measurement and the effective lateral relaxation time (T2 * rest) at rest,
Total hemoglobin measured and input by the brain activity measuring device ([total-Hb]), change in total hemoglobin relative to rest ( [total-Hb]) , change in blood oxygenation rate (△ Y) A recording step for recording at least in the recording unit;
These numbers can be any of the following formulas:
△ S / Srest = (TE ・ T2 * rest) ・ {2 △ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
Or
△ S / Srest = (TE ・ T2 * rest) ・ {△ Y / (1-Yrest) ― △ [total-Hb] / [total-Hb] rest}
(However, “rest” means “resting (resting)”, [total-Hb] rest is “total amount of hemoglobin at rest”, and “Yrest” is the oxygenation rate of resting hemoglobin. Indicate)
Applying the calculation to the calculation unit, the calculation unit calculates the functional MRI (fMRI) signal ΔS / Srest (the ratio of the change from rest to the MRI signal intensity at rest) by the calculation unit. Computer software characterized by having.
fMRI及び近赤外線を用いて並行して脳活動の計測を行ない、
該fMRI測定による信号強度を経時的に表示するfMRI信号強度表示手段、
該近赤外線測定による細静脈でのヘモグロビンの変化を表示する近赤外線細静脈ヘモグロビン変化表示手段、
該近赤外線測定による毛細静脈血管でのヘモグロビンの変化を表示する近赤外線毛細静脈血管ヘモグロビン変化表示手段とを有する
請求項1または2に記載の脳活動計測装置。
Measure brain activity in parallel using fMRI and near infrared,
FMRI signal intensity display means for displaying the signal intensity by the fMRI measurement over time;
A near-infrared venule hemoglobin change display means for displaying a change in hemoglobin in the venule by the near-infrared measurement,
The brain activity measuring device according to claim 1, further comprising a near-infrared capillary venous hemoglobin change display unit that displays a change in hemoglobin in the capillary vein by the near-infrared measurement.
脳活動計測において、
チェッカーボードの反転による視覚刺激を与えて、
少なくともfMRI信号((△S/S)rest)、酸素化ヘモグロビン([oxy-Hb] 及び [oxy-Hb])、脱酸素化ヘモグロビン([deoxy-Hb] 及び△ [deoxy-Hb])及び全ヘモグロビン量([total-Hb] (= [oxy-Hb]+[deoxy-Hb]) 及び△ [total-Hb] (= [oxy-Hb]+ [deoxy-Hb]))のいずれかを測定して、脳機能解析に用いる
請求項3に記載の脳活動計測方法。
In brain activity measurement,
Give visual stimulus by reversing the checkerboard,
At least fMRI signal ((ΔS / S) rest), oxygenated hemoglobin ([oxy-Hb] and [oxy-Hb]) , deoxygenated hemoglobin ([deoxy-Hb] and △ [deoxy-Hb]) and total hemoglobin ([total-Hb] (= [oxy-Hb] + [deoxy-Hb]) And [total-Hb] (= Δ [oxy-Hb] + Δ [deoxy-Hb])) is used for brain function analysis.
JP2001297839A 2001-09-27 2001-09-27 Method and apparatus for measuring brain activity by near infrared spectroscopy Expired - Lifetime JP3740527B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2001297839A JP3740527B2 (en) 2001-09-27 2001-09-27 Method and apparatus for measuring brain activity by near infrared spectroscopy

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2001297839A JP3740527B2 (en) 2001-09-27 2001-09-27 Method and apparatus for measuring brain activity by near infrared spectroscopy

Publications (2)

Publication Number Publication Date
JP2003093390A JP2003093390A (en) 2003-04-02
JP3740527B2 true JP3740527B2 (en) 2006-02-01

Family

ID=19118839

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2001297839A Expired - Lifetime JP3740527B2 (en) 2001-09-27 2001-09-27 Method and apparatus for measuring brain activity by near infrared spectroscopy

Country Status (1)

Country Link
JP (1) JP3740527B2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3635332B2 (en) * 2003-03-20 2005-04-06 独立行政法人情報通信研究機構 Head wearing equipment
JP4517111B2 (en) * 2004-06-07 2010-08-04 独立行政法人情報通信研究機構 Brain function measuring device, brain function measuring method, and brain function measuring program
WO2011153521A2 (en) * 2010-06-04 2011-12-08 Mclean Hospital Corporation Multi-modal imaging of blood flow
WO2012150657A1 (en) 2011-05-02 2012-11-08 パナソニック株式会社 Presence-of-concentration-deducing device and content evaluation device
JP6270031B2 (en) * 2014-01-20 2018-01-31 学校法人 久留米大学 MRI index estimation method and biometric apparatus

Also Published As

Publication number Publication date
JP2003093390A (en) 2003-04-02

Similar Documents

Publication Publication Date Title
Gagnon et al. Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements
Wobst et al. Linear aspects of changes in deoxygenated hemoglobin concentration and cytochrome oxidase oxidation during brain activation
Toronov et al. The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal
Huppert et al. A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans
Kainerstorfer et al. Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy
Seiyama et al. Circulatory basis of fMRI signals: relationship between changes in the hemodynamic parameters and BOLD signal intensity
Funane et al. Quantitative evaluation of deep and shallow tissue layers' contribution to fNIRS signal using multi-distance optodes and independent component analysis
Tong et al. Time lag dependent multimodal processing of concurrent fMRI and near-infrared spectroscopy (NIRS) data suggests a global circulatory origin for low-frequency oscillation signals in human brain
Fukunaga et al. Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages
Firbank et al. A theoretical study of the signal contribution of regions of the adult head to near-infrared spectroscopy studies of visual evoked responses
Gratton et al. Removing the heart from the brain: compensation for the pulse artifact in the photon migration signal
Herrmann et al. Enhancement of activity of the primary visual cortex during processing of emotional stimuli as measured with event‐related functional near‐infrared spectroscopy and event‐related potentials
Sorelli et al. Assessment of cutaneous microcirculation by laser Doppler flowmetry in type 1 diabetes
Alderliesten et al. Simultaneous quantitative assessment of cerebral physiology using respiratory-calibrated MRI and near-infrared spectroscopy in healthy adults
Gursul et al. Nociception and the neonatal brain
JP5433772B2 (en) Biological light measurement device
Aletti et al. Deep and surface hemodynamic signal from functional time resolved transcranial near infrared spectroscopy compared to skin flowmotion
Strangman et al. Near-infrared spectroscopy and imaging for investigating stroke rehabilitation: test-retest reliability and review of the literature
Cooper et al. The utility of near-infrared spectroscopy in the regression of low-frequency physiological noise from functional magnetic resonance imaging data
Scholkmann et al. Cerebral hemodynamic and oxygenation changes induced by inner and heard speech: a study combining functional near-infrared spectroscopy and capnography
JP4559417B2 (en) Biological light measuring device and program
Han et al. Wavelet coherence analysis of prefrontal tissue oxyhaemoglobin signals as measured using near-infrared spectroscopy in elderly subjects with cerebral infarction
Gao et al. Cerebral autoregulation in response to posture change in elderly subjects-assessment by wavelet phase coherence analysis of cerebral tissue oxyhemoglobin concentrations and arterial blood pressure signals
Kodama et al. Analgesic effects of compression at trigger points are associated with reduction of frontal polar cortical activity as well as functional connectivity between the frontal polar area and insula in patients with chronic low back pain: a randomized trial
Bu et al. Effects of physical training on brain functional connectivity of methamphetamine dependencies as assessed using functional near-infrared spectroscopy

Legal Events

Date Code Title Description
RD02 Notification of acceptance of power of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7422

Effective date: 20040416

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20040607

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20040805

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20041102

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20041215

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20050510

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20050607

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20050726

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20051004

R150 Certificate of patent or registration of utility model

Free format text: JAPANESE INTERMEDIATE CODE: R150

S533 Written request for registration of change of name

Free format text: JAPANESE INTERMEDIATE CODE: R313533

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350