CN110507327A - The method of oxygen metabolism rate is dynamically measured under a kind of low-oxygen environment - Google Patents
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Abstract
The present invention relates to magnetic resonance imagings and physio-parameter detection field, and in particular to the method for oxygen metabolism rate is dynamically measured under a kind of low-oxygen environment: on the one hand, the influence in conjunction with dHb in artery and venous blood for BOLD signal establishes new model；On the other hand, the relationship between the M under the M and normal oxygen conditions under low-oxygen environment is established.Method proposed by the present invention is able to solve existing dynamic measurement CMRO2Model the problem of being not applied for low-oxygen environment, to study brain function under low-oxygen environment and cerebral disease provides new tool.
Description
Technical field
The present invention relates to magnetic resonance imagings and physio-parameter detection field, and in particular to dynamically measures under a kind of low-oxygen environment
The method of oxygen metabolism rate.
Background technique
The oxygen metabolism rate (CMRO2) of brain characterizes oxygen consumption of the brain tissue of unit volume within the unit time, is
The important physiological parameter of brain.CMRO2 has been demonstrated and a variety of cerebral diseases (such as headstroke, brain tumor and alzheimer's disease)
It is closely related.Dynamic measurement CMRO2 helps to probe into working mechanism of the brain in the task of execution.
Based on magnetic resonance imaging (MRI) technology, Davis et al. proposition is utilized in the method for traditional dynamic measurement CMRO2
Model (hereinafter referred to as " Davis model ")1.Davis model hypothesis brain is under normal oxygen environment, in other words arterial blood
Oxygen saturation (Ya) be similar to 1, the concentration of deoxyhemoglobin (dHb) is similar to 0.Brain blood volume is obtained by MRI technique
(CBV) signal, brain blood flow (CBF) signal, Blood oxygen level dependence (BOLD) signal and correction parameter M, establish equation
Extrapolate CMRO2 signal1。
However, brain is in low-oxygen environment under plateau or specific cerebral disease environment, Ya is lower than 0.9 in other words.This
When, Davis model is no longer applicable in, and reason has two.First, under the hypothesis of Davis model Ya~1, BOLD signal main source
The concentration of dHb in venous blood changes1, that is, have ignored the contribution of arterial blood.And under low-oxygen environment, in artery and venous blood
DHb all BOLD signal is contributed.Second, M is to utilize sucking high-carbon acid gas under normal oxygen conditions in Davis model
CBF rises when body, but the constant physiological phenomenon measurement of CMRO2 obtains1.And under low-oxygen environment, which is broken, low
M under oxygen environment can not be measured according to original method.
Summary of the invention
In order to solve the problems, such as that Davis model is not suitable for low-oxygen environment, the present invention is based on MRI technique, propose that one kind exists
The method of CMRO2 is dynamically measured under low-oxygen environment.On the one hand, in conjunction with influence of the dHb for BOLD signal in artery and venous blood
Establish new model；On the other hand, the relationship between the M under the M and normal oxygen conditions under low-oxygen environment is established.The present invention
The method of proposition is able to solve the problem of Davis model is not applied for low-oxygen environment, be low-oxygen environment under research brain function and
Cerebral disease provides new tool.
A kind of method dynamically measuring CMRO2 under low-oxygen environment proposed by the present invention, including following model scheme:
In following scheme, defines subscript 0, a and v and respectively represent quiescent condition, artery and vein；Subscript norm and
Hypo respectively represents normal oxygen and hypoxia；Alphabetical δ representation signal is under task status relative to the percentage under quiescent condition
Than, such as δ Β OLD=BOLD/BOLD0-1。
Boxerman et al. proposes the variable quantity of effective lateral relaxation time,With the oxygen saturation (Y) in blood
And the relationship between CBV is2:
Wherein A is the constant determined by field strength and sample properties；β is a characterizationBetween blood and tissue
The constant of the relationship of susceptibility difference, β=1.5.
Davis et al. propose δ BOLD andBetween relationship be1:
Wherein TE is the echo time.
In conjunction with formula (1) and (2), can obtain:
Blood is divided into arterial blood and venous blood (blood of capillary is prorated in plasma viscosity)3, Y
It can indicate are as follows:
Y=α Ya+(1-α)Yv, (4)
Wherein α is arterial blood fraction, α=0.3.
According to Fick's law, CMRO2, CBF and artery and vein oxygen content (CaO2And CvO2) between relationship may be expressed as:
CMRO2=CBF (CaO2-CvO2). (5)
Wherein CaO2And CvO2It can further indicate that are as follows:
WhereinRepresent the oxygen carrying capacity of hemoglobin (Hb)；[Hb] represents the concentration of Hb；YaAnd YvIt respectively represents dynamic and static
The oxygen saturation of arteries and veins blood；PaO2And PvO2Respectively represent the partial pressure of oxygen of plasma viscosity；ε represents the solubility of oxygen in blood.
In formula (6) and (7), first item represents the oxygen in conjunction with Hb on the right side of equation, and Section 2 represents the oxygen of dissolution in blood
Gas, the latter < < the former, therefore can be ignored.
In conjunction with formula (5), (6) and (7), can obtain:
In conjunction with formula (3), (4) and (8), can derive:
Formula (1)-(9) are suitable for normal oxygen and low-oxygen environment.
Under normal oxygen conditions, by Ya=YA, 0=1 brings formula (9) into, can obtain
Wherein δ CBVnorm、δCBFnormWith δ BOLDnormIt can be obtained by MRI means measurement, MnormSucking can be passed through
The mode measurement of high-carbon acid gas, hyperoxia gas or high carbon acid, high-oxygen gas mixture body obtains1。
M under low-oxygen environmenthypoCan not measure to obtain by way of sucking high carbon acid, but can by formula (3) and
(4) it connects:
Wherein It can be surveyed by MRI means
It measures,It can be obtained by instrument for detecting sphygmus and blood oxygen saturation in the measurement of finger end.
Acquire MhypoIt afterwards, can be by MhypoBring formula (9) into, a kind of method for obtaining dynamically measuring CMRO2 under hypoxemia are as follows:
A kind of method dynamically measuring CMRO2 under low-oxygen environment proposed by the present invention, including following operating procedure (see
Fig. 1):
(1) mode that user sucks high-carbon acid gas, hyperoxia gas or high carbon acid, high-oxygen gas mixture body measures Mnorm。
(2) arterial oxygen saturation under the normal oxygen of user, quiescent condition is obtainedSvo2With brain blood volume signals
(3) arterial oxygen saturation under user's hypoxemia, quiescent condition is obtainedSvo2
Brain blood volume signalsBrain Blood oxygen level dependence signalThe variation percentage of signal of brain's blood streamWith arterial oxygen saturation under hypoxemia, completion particular task stateBrain blood volume signals CBVhypo, brain blood
Oxygen level relies on signal BOLDhypo, signal of brain's blood stream variation percentage CBFhypo；
(4) it is calculated based on above-mentioned acquired each signal value and corrects parameter M under low-oxygen environmenthypo；
(5) based on M obtained in each signal value and step (3) acquired under above-mentioned low-oxygen environmenthypoCalculate hypoxemia ring
Variation percentage δ under cerebral metabolism rate of oxygen of the user when completing particular task is relative to quiescent condition under border
CMRO2hypo。
Further, high-carbon acid gas, the mode of hyperoxia gas or high carbon acid, high-oxygen gas mixture body are sucked in the above method
Measure MnormMethod referring to Davis et al.1, Chiarelli et al.4Or Gauthier et al.5Method.
Further, above method medium sized vein blood oxygen saturation is measured by MRI means or priori knowledge obtains (being shown in Table
1)；Arterial oxygen saturation is obtained by instrument for detecting sphygmus and blood oxygen saturation in the measurement of finger end.
Further, above method deutocerebral region δ BOLD, δ CBF and δ CBV signal are obtained by MRI means measurement.
Further, high-carbon acid gas described in step (1) is by 5%CO2, 21%O2And 74%N2Composition.
Further, low-oxygen environment Digital arteries blood oxygen level described in step (2) is lower than 90%.
Detailed description of the invention
Fig. 1 is the flow chart of the invention that CMRO2 is measured under low-oxygen environment.
Fig. 2 is that CMRO2 result of variations caused by visual task compares under normal oxygen conditions and low-oxygen environment.
Specific embodiment
In the following description, a large amount of concrete details are given in order to which those skilled in the art are more thorough to the present invention
The understanding at bottom.It is to be understood that disclosed herein is only a kind of representative preferred embodiment.Obviously, the present invention is simultaneously
It is not limited to any specific structure described herein, function, Apparatus and method for, it is possible to have other embodiments, or
It is the combination of other embodiments.Element number described in the present invention it is also contemplated that be multiple, unless explicitly limited for
Odd number.In addition, to avoid other examples from obscuring with the present invention, for some technical characteristics well known in the art and carefully
Section is not described.
Embodiment:
Gaseous environment: the high-carbon acid gas in this example is by 5%CO2, 21%O2And 74%N2Be made, low-oxygen environment by
12%O2And 88%N2It is made, is separately stored in gas cylinder, the non-duplicate formula that user is worn is passed through with the flow of 15L/min
Breathing mask.
Experimental duties: this example uses the visual task of block design, by 12 seconds prescans and 7 60 seconds tranquillization and view
Feel the block composition that stimulation is alternately present.Visual stimulus is present on the computer screen between magnet, is reflected by a mirror
Into the user's eye to lie low on scanning bed.Within the tranquillization period, user is it is seen that a black screen and screen
The cross blinkpunkt of central white.Within the visual stimulus period, the circular black and white gridiron pattern that user sees, each
With the frequency scintillation of 1,4 or 8Hz in the block of visual stimulus.During visual task, user needs the task at 432 seconds
It keeps opening eyes in the process, and watches the center of screen attentively.
MRI scan: in this example, δ CBV, δ CBF and δ BOLD are mentioned by 3 T MRI scan systems using Yang et al.
Vascular space occupation rate (VASO) out, the free label (ASL) of artery and BOLD signal synchronous collection sequence obtain6.For view
Feel task is chosen across commissura anterior, postcommissure and extends to one layer of primary visual cortex (V1) and be acquired.Specifically sweep
Retouch parameter are as follows: visual field size=260x 260mm2, the TE of matrix size=64x64, thickness=6mm, three signals is respectively
9.4ms, 11.6ms and 28.1ms, inversion thickness=102mm, the reversing time (TI) of CBV and CBF signal be respectively 680ms and
1200ms, repetition time (TR)=2000ms.
MRI signal processing: pass through ring in first time/second/third time echo acquirement label and non-marked image
Around be averaged/subtracting each other/average method7Obtain VASO/ASL/BOLD image.It is linear to the image removal acquired during visual task
Drift.Space smoothing is carried out to the image acquired during all tasks.Reaction mind is found by general linear model (GLM)
Voxel through activating.The definition of area-of-interest (ROI) is under low-oxygen environment, and VASO, ASL and BOLD signal all significantly swash
Voxel living.The time series and difference of his/her VASO, ASL and BOLD in the task of completion are extracted from the ROI of user
It is normalized into the baseline of corresponding signal.The definition of baseline is the average value at first minute all time point of each group task.For
Hemodynamics is avoided to respond the influence for result, preceding 8s data collected after each stimulation task starts are moved
It removes, the average value of remaining data is counted as δ VASO, δ CBF caused by the stimulation task or δ BOLD response.δ CBV passes through δ VASO root
It is calculated according to the method for Lin et al.8。
Further, by the δ CMRO in formula (10)20 is replaced with, and substitutes into what the measurement in high-carbon acid gas task obtained
Then the M under normal oxygen conditions is calculated in δ CBV, δ CBF and δ BOLDnorm.M under low-oxygen environmenthypoIt is to pass through formula
(12) it is calculated.In this example, the parameter reference table 1 in formula (11) and (12).Obtaining MnormAnd MhypoAfter,
δ CMRO under normal oxygen conditions and low-oxygen environment2Formula (10) can be passed through respectively and (12) are calculated.
Parameter list in 1 the present embodiment of table in formula (11) and (12)
Fig. 2 is to measure the variation of CMRO2 caused by the visual task knot under normal oxygen conditions and low-oxygen environment in this example
Fruit is compared.The variation of CMRO2 caused by visual task becomes lower than CMRO2 caused by visual task under normal oxygen conditions under low-oxygen environment
Change, this is consistent with the result for using existing mathematical modeling technique to be assessed9, illustrate the feasibility of this method.
Bibliography:
1 Davis TL,Kwong KK,Weisskoff RM,Rosen BR.Calibrated functional MRI:
Mapping the dynamics of oxidative metabolism.Proceedings of the National
Academy of Sciences 1998；95:1834–1839.
2 Boxerman JL,Bandettini PA,Kwong KK,Baker JR,Davis TL,Rosen BR et
al.The intravascular contribution to fMRI signal change:Monte Carlo modeling
and diffusion- weighted studies in vivo.Magn Reson Med 1995；34:4–10.
3 Lin W,Paczynski RP,Celik A,Kuppusamy K,Hsu CY,Powers
WJ.Experimental hypoxemic hypoxia:changes in R2*of brain parenchyma
accurately reflect the combined effects of changes in arterial and cerebral
venous oxygen saturation.Magn Reson Med 1998；39:474–481.
4 Chiarelli PA,Bulte DP,Wise R,Gallichan D,Jezzard P.A calibration
method for quantitative BOLD fMRI based on hyperoxia.NeuroImage 2007；37:808–
820.
5 Gauthier CJ,Hoge RD.A generalized procedure for calibrated MRI
incorporating hyperoxia and hypercapnia.Human Brain Mapping 2013；34:1053–
1069.
6 Yang YEA,Gu H,Stein EA.Simultaneous MRI acquisition of blood
volume,blood flow, and blood oxygenation information during brain
activation.Magn Reson Med 2004；52: 1407–1417.
7 Lu H,Donahue MJ,van Zijl PCM.Detrimental effects of BOLD signal in
arterial spin labeling fMRI at high field strength.Magn Reson Med 2006；56:
546–552.
8 Lin A-L,Fox PT,Yang YEA,Lu H,Tan L-H,Gao J-H.Evaluation of MRI
models in the measurement of CMRO2 and its relationship with CBF.Magn Reson
Med 2008；60:380– 389.
9 Rodrigues Barreto F,Mangia S,Garrido Salmon CE.Effects of reduced
oxygen availability on the vascular response and oxygen consumption of the
activated human visual cortex.J Magn Reson Imaging 2017；46:142–149.
Claims (9)
1. dynamically measuring the method for oxygen metabolism rate under a kind of low-oxygen environment, which comprises the following steps:
(1) it obtains and corrects parameter M under user's normal oxygen conditionsnorm；
(2) arterial oxygen saturation under the normal oxygen of user, quiescent condition is obtainedSvo2And brain
Blood volume signals
(3) arterial oxygen saturation under user's hypoxemia, quiescent condition is obtainedSvo2Brain blood body
Product signalBrain Blood oxygen level dependence signalThe variation percentage of signal of brain's blood streamWith it is low
Oxygen completes arterial oxygen saturation under particular task stateBrain blood volume signals CBVhypo, brain Blood oxygen level dependence letter
Number BOLDhypo, signal of brain's blood stream variation percentage CBFhypo；
(4) it is calculated based on above-mentioned acquired each signal value and corrects parameter M under low-oxygen environmenthypo；
(5) based on M obtained in each signal value and step (3) acquired under above-mentioned low-oxygen environmenthypoCalculating should under low-oxygen environment
Cerebral metabolism rate of oxygen of the user when completing particular task relative to quiescent condition under variation percentage δ CMRO2hypo。
2. method as described in claim 1, which is characterized in that M in step (1)normIn user sucking high-carbon acid gas or
It is measured under conditions of hyperoxia gas or high carbon acid, high-oxygen gas mixture body.
3. method as described in claim 1, which is characterized in that the brain Blood oxygen level dependence signal, signal of brain's blood stream and brain
Blood volume signals are obtained by the measurement of MRI means.
4. method as described in claim 1, which is characterized in that the Svo2 is measured by MRI means or elder generation
Test knowledge acquisition.
5. method as claimed in claim 4, which is characterized in that according to priori knowledge,For 0.6-0.7,For 0.5-
0.6。
6. method as described in claim 1, which is characterized in that the arterial oxygen saturation is existed by instrument for detecting sphygmus and blood oxygen saturation
The measurement of user's finger end obtains.
7. method as described in claim 1, which is characterized in that the low-oxygen environment Digital arteries blood oxygen level is lower than 90%.
8. method as described in claim 1, which is characterized in that step (4) is calculated by the following formula Mhypo:
Wherein, α is arterial blood fraction, α=0.3；β is the variable quantity of an effective lateral relaxation time of characterizationWith blood
The constant of the relationship of susceptibility difference, β=1.5 between liquid and tissue.
9. method as described in claim 1, which is characterized in that step (5) is calculated by the following formula δ CMRO2hypo:
,
Wherein, δ BOLDhypoFor the variation percentage of brain Blood oxygen level dependence signal,
δCBFhypoFor the variation percentage of signal of brain's blood stream,δCBVhypoFor brain blood volume letter
Number variation percentage,
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