CN1281345A - Apparatus for fluid administration - Google Patents

Apparatus for fluid administration Download PDF

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Publication number
CN1281345A
CN1281345A CN98811897.1A CN98811897A CN1281345A CN 1281345 A CN1281345 A CN 1281345A CN 98811897 A CN98811897 A CN 98811897A CN 1281345 A CN1281345 A CN 1281345A
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China
Prior art keywords
fluid
inlet
valve
reservoir
gas
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CN98811897.1A
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Inventor
诺伯特·韦勒
巴尔萨泽·埃伯利
迈克尔·埃伯特
蒂诺·格罗斯曼
沃纳·海尔
汉斯-乌尔里克·考克佐
拉斯·劳尔
克劳斯·马克斯塔勒
厄恩斯特·奥滕
莱因哈德·瑟考
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/02Inhalators with activated or ionised fluids, e.g. electrohydrodynamic [EHD] or electrostatic devices; Ozone-inhalators with radioactive tagged particles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/05Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/08Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/0813Measurement of pulmonary parameters by tracers, e.g. radioactive tracers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/0015Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors
    • A61M2016/0018Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical
    • A61M2016/0021Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical with a proportional output signal, e.g. from a thermistor

Abstract

The invention provide an apparatus for fluid administration comprising: a variable volume fluid reservoir and a fluid conduit leading therefrom to a fluid outlet, a first fluid inlet and a second fluid inlet; a first detector arranged to detect fluid flow between said conduit and said reservoir; a first valve arranged to permit or prevent fluid flow from said first inlet through said conduit into said reservoir; a second valve which in a first setting permits fluid flow from said second inlet through said conduit to said outlet and prevents fluid flow from said reservoir through said conduit to said outlet and in a second setting permits fluid flow from said reservoir through said conduit to said outlet and prevents fluid flow from said second inlet through said conduit to said outlet; a second detector arranged to detect fluid flow into said conduit from said second inlet; and an activator arranged to control the operation of said first and second valves.

Description

The device that convection cell is controlled
The present invention relates to a kind of device (calling applicator (applicator) in the following text), its suitable conveyance fluid wadding (bolus), for example wadding of liquid or gas; Sometimes can comprise a kind of adulterated discontinuous phase, solid granulates for example, drop, capsule grain (for example micelle, liposome, microvesicle, microsphere etc.) and other analog.Especially in the respiratory system of the suitable animal (for example mammal, reptile and birds) that the gas wadding is transported to people or breathe air of this applicator.More particularly, the suitable delivery of hyperpolarized gas wadding of this applicator.
In the magnetic resonance imagine (MRI), adopt the image that produces the goal in research thing from the NMR signal of the nuclear of the non-zero nuclear spin in the goal in research thing.In routine MRI, be proton to the active nuclear of signal (imaging nuclear), extensively be proton in fact.Population difference (polarization) between the different IPs spin states of the intensity of MR signal and imaging nuclear is proportional, and this distributes by Boltzmann (Boltzmann) again and is determined, depends on magnetic field and temperature.For I=1/2 imaging nuclear, equivalence polarization P 0Can calculate by following formula:
Its approximate expression is: P o ≈ μB o KT In the formula: N α is a spin states α (for example+1/2) population of nuclear down;
N β is another spin states α (for example-1/2) population of nuclear down;
γ is the magnetic rotation rate of nuclear;
H is 2 π/Planck's constant;
K is a Boltzmann constant;
B 0Be magnetic field intensity (or density of line of magnetic force);
T is an absolute temperature;
μ is the magnetic core dipole moment.
Recent findings might increase the MR signal intensity by the polarization value (hyperpolarization) that imaging nuclear polarization to is higher than equivalence value (for the magnetic field intensity and the running temperature of MR imaging device).
One of approach that obtains hyperpolarization is 3He optical pumping (for example referring to Schearer et al.Phys.Rev.Letters 10:108-110 and Eckert et al.Nucl.Instr, and Methods A320:53-65 (1992)). 3The nuclear spin I=1/2 of He, this can be used as imaging nuclear (for example referring to US-A-5642625 in MRI, US-A-5612103, US-A-5545396, WO95/27438, WO97/37239, Song et al.J.Mag.Res.A 115:127-130 (1995) and Middleton et al.Mag.Res.Med.33:271-275 (1995)).
Exist in general 3Among the He MRI, hyperpolarization 3The He wadding is transported in the respiratory tract of object, for example enters in trachea, lung and the cellular space, from 3The MR signal of He is used to produce the image of lung.Because intraorganic nature in health 3Can ignore in the He source, therefore can ignore from the signal of other body regions except that respiratory tract.
Helium atom has different performances to oxygen and nitrogen (key component of the air of breathing usually for object), diffusivity for example, if 3The He wadding can not be different from air greatly and be distributed to respiratory tract, and so ideal situation is the very fraction that air only accounts for whole suction volume.
In addition, 3The He wadding can be carried in the different phase of breathing, and can produce outstanding respiratory tract different piece so, the image of for example cellular space or trachea.
Moreover production and supply quantity is much higher than the hyperpolarization that produces the single image requirement 3He gas suits, and it is desirable to like this, but can adopt the polarized gas source that comprises extremely many gases to make the gas wadding with repeat size.Is ideal in the high-caliber repeatability aspect wadding size and the position two to systemic medical research and case accumulation.
Therefore, just need a kind of device, the moment that it can volume be in accordance with regulations stipulated in breathing stroke will polarize 3The He wadding is transported in the respiratory tract of object.
An object of the present invention is to provide the device that a kind of convection cell is controlled, it comprises a variable-volume fluid reservoir and the mozzle from a fluid issuing of fluid reservoir guiding; A first fluid inlet and one second fluid intake; One first detector is used to survey the fluid stream between described conduit and described reservoir; One first valve, be used to allow or prevent fluid from described first the inlet flow to described reservoir by described conduit; One second valve, it is set the position first and allows that fluid flows to described outlet and prevents that fluid from flowing to described outlet from described reservoir by described conduit by described conduit from described second inlet, sets the position second and allows that fluid flows to described outlet by described conduit and prevents that fluid from flowing to described outlet from described second inlet by described conduit from described reservoir; One second detector is used to survey the fluid that flows in the described conduit from described second inlet and flows; With an activator, be used to control the operation of described first and second valves.
Device of the present invention i.e. " applicator " mainly is the respiratory tract that is used for hyperpolarized gas is transported to object, also in this scope, describe below, yet it also is fit to carry other single-phase or heterogeneous waddings as above-mentioned, for example: liquid, solid-liquid suspension thing, solution-air diffusate etc.Yet hereinafter " liquid " only refers to gas, and flow of liquid and liquid input etc. refers to air-flow or gas input etc.
The main target of applicator of the present invention is to introduce different gas in breathing stroke, should avoid the mixing of gas with various in this case to a great extent.Fig. 1 illustrative in the accompanying drawing is used for the device of two kinds of gas with various.Inject first kind of gas 2, for example air in the flexible pipe 1 earlier.Inject second kind of gas 3, for example hyperpolarization subsequently 3He is injecting original gas 4.Component in flexible pipe between respiratory period is inhaled into, and supposes not take place owing to disturbance or owing to flowing velocity is too fast mutual blended words, and this gas sequence does not just enter pulmonary mutually with mixing so.According to position and the volume of gas wadding 3 in flexible pipe, thereby the gas of determining volume might be placed into specific part in the pulmonary.
Applicator of the present invention can advantageously be equipped with one the 3rd valve, and it is used to prevent flow back into described second valve from described outlet, for example by it being directed to one second outlet (for example opening) or being directed to one second reservoir, for example collects 3He is to utilize once more.
The 3rd valve is preferably settled the backflow that is used to prevent when object is exhaled and can be controlled by applicator, maybe can be one automatically by the driven valve of handling at the air-flow in exit.Alternatively, described second valve can have one the 3rd to set the position, and wherein the air-flow from outlet is prevented from entering first reservoir or arrives second inlet, but is directed into one second outlet or one second reservoir; At the 3rd valve described in this layout is unnecessary.
Described first reservoir can be the reservoir of variable volume arbitrarily, for example has the bucket of moveable piston (promptly as in a syringe), flexible bag, corrugated tube etc.Yet in a suitable especially embodiment, reservoir is a kind of expansion type container (collapsible corrugated tube made from plastics for example for example, be preferably not the thin film of saturating helium or scribble a kind of like this plastics of thin film), it is placed in the inflexible container, the latter has a passage, and first detector joins therewith.The gas that flows to or flow out the expansion type container causes that corresponding air communication crosses this passage, thereby allows that indirect detection and measurement flow to and flow out the air-flow of container when expanding.
In a particularly preferred embodiment of applicator, the gas that flows to second inlet is from respiratory organ.Particularly preferably being second valve in this embodiment is the second setting position, should reboot to exert pressure from the air-flow of respiratory organ to the outside of variable-volume reservoir, thus the stream pressure from this reservoir to object should with more preceding or after the stream pressure from the respiratory organ to the object identical.In addition preferably, applicator should comprise should detector, for example utilizes the differential pressure detector, and it surveys when the variable-volume reservoir arrives its minimum volume, and second valve can be got back to it and first set the position in view of the above.
In some occasion, or independently or mix ground to annotate the different fluid of executing from the variable-volume reservoir (gas) be ideal.In this case, should be conduit another (the 3) inlet and another (the 4th) valve be provided, the latter prevent or allow air-flow from described the 3rd inlet by conduit with enter the variable-volume reservoir.Applicator can be equal to operation when annotating the fluid execute from first inlet in that this other fluid is annotated the operation of executing by the variable-volume reservoir, activator also preferably is set is used to control the 4th valve.
In applicator of the present invention, the operation of activator is preferably controlled according to the setting position (for example ideal wadding size and position) that signal and operator from detector import by controller.
So in one embodiment, the invention provides a kind of device, be used for gaseous material accurately annotated and execute pulmonary and respiratory tract, this device is equipped with following parts:
-one first inlet (203) is used to introduce first kind of vaporous material, especially a kind of gas that polarized atom (atomic nucleus) arranged;
-one metering device (230,231), it is connected with this first inlet (203), the volume of first kind of gaseous material that be employed is measured control;
-one second inlet (301,305) is used to introduce second kind of vaporous material;
-one measuring device (304) is used to measure the volume through second gaseous material of the second inlet introduction;
-one outlet (241,243) is used for first and second kinds of gaseous materials;
-one changeover valve (240), its end is connected with second inlet (301,305) with metering device (230,231), the other end is connected with outlet (241,243), can select to export (241,243) in the first valve setpoint position and be connected, can select to export (241,243) in the second valve setpoint position and be connected with metering device (230,231) with second inlet (301,305);
-metering device (230,231) has an expansion type container (231) that joins with first inlet, be placed in the housing (230), this housing provides at least one passage (235,236), another measuring device (232,244) is connected with this passage, measures at container to flow out the gas of housing (230) between (231) phase of expansion and/or flow to the gas of housing (230) during container (231) shrinks;
-one control unit (220), it is connected with changeover valve (240) with two measuring devices (304,232,244),
-as the function of amount of gas discharge from the housing (230) of metering device (230,231) and that measured by described another measuring device (232,244), first kind of gaseous material of this control unit control flows to the volume of the expansion type container (231) of metering device (230,231)
-as the function of second kind of gaseous material quantity being measured by first measuring device (304) or after the time of one section setting used up, this control unit was transformed into the second valve setpoint position with changeover valve (240) from the first valve setpoint position,
-as the function of the amount of gas in the housing of being measured by described another measuring device (232,244) (230) that flows to metering device (230,231), this control unit is transformed into the first valve setpoint position with changeover valve (240) from the second valve setpoint position.
The valve of applicator, conduit etc. are all preferably constructed like this, make that the center line of stream stream behind second valve is dominant, and promptly avoid dispersing the disturbance of wadding, and the disturbance meeting mixes different gas.
This applicator can be used to allow different wadding volumes ideally and allow the position that wadding is placed in any desired of whole breathing stroke.This applicator is preferred for allowing that independent notes are executed or the series notes are executed in addition, and wherein for example wadding volume, wadding position etc. can change.Moreover it is desirable to, this applicator is used to allow that single gas wadding of planting gas or mist controls, this mist for example be hyperpolarized gas such as 3The mist of gas such as the nitrogen of He and a kind of lax (relaxation) time that can not shorten this hyperpolarized gas.In this case, non-lax gas (nitrogen N for example 2) at first inject the variable-volume reservoir usually, then immediately with a selected amount of hyperpolarized gas 3He mixes mutually.Dilution 3The long wadding of He then can be controlled, and for example is used for aeronomy.
It is desirable to, the breathing of object promptly should not interfered or end significantly to the operation of applicator significantly by the production of gas sequence of outlet.
In addition, gases used, for example 3He may be expensive, and this applicator decision design reuses them.
From the medical science viewpoint, breathe for three kinds and make a clear distinction between good and evil:
(1) freedom under the monomer self-efforts (not interrupted) autonomous respiration;
(2) the auxiliary autonomous respiration of respiratory organ;
(3) breathing of controlling by respiratory organ.
Respiratory organ can come control breathing by pressure control or flow-control; Promptly in respiratory form (3), intake period pressure or throughput adjusted.For autonomous respiration, the inhaled air volume changes at any time, and for the volume control breathing that respiratory organ is controlled, always introduces identical breathing gas volume.The present invention in this explanation can be used for all three kinds of respiratory forms.
To introducing hyperpolarization of the present invention 3The embodiment of He gas is right 3He, several characteristic is ideal in addition, will be in short summary 3Explanation after the specific characteristic of He MRI.
3The He atomic nucleus carries the spin of overstating subnumber I=1/2, and magnetic moment μ accompanies with it.These magnetic moments make the magnetic line of force of own parallel or antiparallel and external magnetic field when having the external magnetic field.Yet, at atom with have between the atom of antiparallel magnetic moment a kind of balance is arranged with parallel magnetic moment.This can be illustrated by the polarization equation that provides previously, and B0 is magnetic field intensity (being density of line of magnetic force or rather) in the equation; K is a Boltzmann constant, equals 1.38 * 10 -23T is an absolute temperature, K.Right 3He, magnetic core dipolemoment=1.075 * 10 -26Am 2, therefore to B 0The MRI device of=1.5 teslas and T=310K, polarization P=3.8 * 10 -6To the gas density under the normal condition, i.e. p=2.33 * 10 19Atom/cm 3(is that 310K and gas pressure are 1.013 crust in temperature), this hypopolarization is to obtain the image of gas at hollow space by MRI.The MR magnetic resonance signal too a little less than.
Yet under the downfield of room temperature and milli tesla (mT) magnitude, 3The He polarization can be lifted near value 1, promptly is higher than Boltzmann equivalence polarization far away.This technology is called " optical pumping ", original and the technology of its physics realizes being described in the following document: Colegrove et al.Phys.Rev.132:2561-2572 (1963), Walters et al.Phys.Rev.Lett.8:439-442 (1962), Schearer et al. Phys.Rev.Lett.10:108-110 (1963), Eckert et al.Nucl.Instr.﹠amp; Meth.A320:53-65 (1992), Eckert et al.Nucl.Instr.﹠amp; Meth.A346:45-51 (1994), Heil et al.Phys.Lett.A201:337-343 (1995), Becker et al.J.of Neutron Research 5:1-10 (1996) and Surkau et al.Nucl.Instr.﹠amp; Meth.A384:444-450 (1997).Obtained the density of the polarization spin p * P of 1 to 2 magnitude, it is higher than at cell tissue water or adipose cell and is organized in B 0The density of the polarization proton in=1.5 teslas and bohr thatch graceful when equivalence.(usually, the polarization proton is used as signal source in MRI, promptly exist 1He-MRI).
To nuclear magnetic resonance, NMR, magnetic moment and B 0Excitation vertically, one of its result induces magnetic resonance signal in a suitable receiving coil.This can cause that polarization reduces, i.e. polarization partly or entirely is damaged, and this depends on that magnetic moment to what extent departs from magnetic direction during the nuclear magnetic resonance, NMR excitation.Be used in 1Available 0.3 to the 1 second characteristic relaxation time T of the graceful polarization of bohr thatch among the He-MRI 1Recover, and 3The He polarization is irretrievably to decay, the characteristic relaxation time T at 10 to 30 seconds 1In decay to well below the graceful equivalence value of bohr thatch from its high initial value in pulmonary.
To in the high-intensity magnetic field 3He MRI, RF excitation (nuclear magnetic resonance, NMR excitation) is according to coming repetition for the required matrix size of image.Yet,, only have a kind of to lung images 3But He gas filling.Therefore, for original polar cos (α), at every turn in each excitation back minimizing order RF excitation 3Magnetic moment during the excitation of He nuclear magnetic resonance, NMR only departs from B slightly 0Axle reaches one for example 2 ° α angle (α=2 °, cos (α)=99.9%).(in other words, adopting the spin response sequence that little reversing angle is arranged, for example RARE sequence, or gradient response sequence, for example FLASH sequence) this point is emphasized restriction during notes are executed 3The demand of the outside hyperpolarization of He gas.
Except the nuclear spin excitation, also have series of factors to damage 3The hyperpolarization of He gas.Put forward some most important factors at this: be derived from the lax of magnetic field gradient, lax on the gas container wall, oxygen ((O 2) sneak into.The relatively vertically gradient (dB in magnetic field in the conventional commercial tomograph 2/ dz)/B 0Be about 10 -7/ cm is very little.Transverse gradients (dB r/ dr)/B 0Similar magnitude is arranged, and the result when gas pressure is 1bar is a T so 1Value: 1 / T 1 = ( 1.75 × 10 4 ( dB r 1 dr B 0 ) 2 ) · 1 cm 2 bar ph It is about 10 -9H-1.
In other words, big like this gradient can not cause any considerable T 1Lax.Even maximum imaging gradient fields of allowing, i.e. (dB r/ dr)/B 0) be about 1.67 * 10 -4/ cm, only causing relaxation rate when p=1bar is 1/T 1=5 * 10 -4/ h, thereby be insignificant.Yet, at the incision of the Magnet of a MRI device, gradient (dB r/ dr)/B 0Approximately up to 10 -1/ cm is about T corresponding slack time 1=21 seconds.So hyperpolarization 3He gas should be rapidly, and (for example in being shorter than one second time Δ t) transported this zone, so that make residual polarization P (P=P 0Exp (Δ t/T 1), P in the formula 0Be initial polarization) maximization, for example hold it in more than 0.95 (95%), thereby keep polarization as much as possible.
Ferromagnetic material is upset uniform magnetic field and is caused extremely strong gradient.Therefore should preferably avoid adopting their materials as the structure applicator.Non-ferromagnetic material keeps magnetic field undisturbed such as for example plastics, titanium or glass, will be suitable in principle.If yet they are as the gas container material, they are different on the wall thickness relaxation property.For long preservation 3The He polarization preferably adopts T slack time 1For the special glass container of a few hours to a couple of days (referring to Heil et al., supra).(referring to Becker et al. (1994) supra) preferably is made of titanium with the contacted valve of hyperpolarized gas.Plastics can adopt, but its adaptability is limited, because 3He may penetrate into their loose structure, and depolarization within it becomes.Typical slack time is in minute scope.Yet in the nuclear spin tomograph, the parts of all motions all are made of plastics usually, cause the interference with nuclear magnetic resonance, NMR chromatographical X-ray image because proved the motion metal parts.
In addition, the paramagnetic impurity that comprises gaseous state oxygen is preferably got rid of from the parts between the reservoir and second valve of applicator at least.Oxygen causes a kind of intensive relaxation effect, has when 299K: T 1 = 2.2 s · Amagat [ O 2 ] (O in the formula 2) be 3Oxygen density in the He gas, unit adds spy (referring to Saam et al., Phys.Rev.A 52:862-865 (1995)) for Ah sign indicating number.Thereby the wall thickness of thick relatively conduit etc. may be ideal, so for example oxygen can be left out by flushing.When with fresh 3When the He source of the gas is received applicator, with a certain amount of (for example about 20mL) 3The He purge 3The He inlet is to remove all air.
In the occasion of applicator being used lived object, the every aspect of the health that should consider.With the contacted parts of the patient's who is checked breathing gas should be preferably disposable or can sterilize or disinfectant.Thereby the material that is used for these " contact " parts should keep dimensionally stable ideally under up to 120 ℃ temperature.
It is desirable to, all parts of applicator are by nonmagnetic substance, nonferrous material especially, and more preferably electrically non-conductive material (for example plastics) is made.It is desirable to moving component especially is made of plastics.
The measuring device of gas flow that flows to when determining pucker ﹠ bloat or flow out the housing of metering device preferably includes an effusion meter, and it is connected with a passage of housing; A differential pressure meter, it is connected with a steam vent of housing, measures the pressure differential between enclosure interior and applicator outlet.Thereby valve (second valve) can the response measurement value and is changed afterwards.
By suitable selection material, applicator of the present invention can be placed in the nuclear magnetic resonance, NMR chromatographical X-ray video camera.(top the discussion what is meant by suitable material selected).
Hyperpolarized gas controlled it is desirable to, the blind area in the device especially between first inlet and the variable-volume reservoir and the zone between this reservoir and outlet, is minimized.This helps to reduce the unnecessary polarization loss that causes because of time delay or wall thickness contact.
Except hyperpolarization 3Beyond the He, applicator also can adopt the gas hyperpolarized gas, for example 129The mixture of Xe and air inclusion hyperpolarization I=1/2 nuclear (for example 13C, 15N and 29Si).
On the other hand, the invention provides a kind of magnetic resonance imagine method, wherein a kind of fluid (is preferably gaseous state, especially for a kind of hyperpolarized gas) the MR preparation supplies to an object with the wadding form, the MR image of at least a portion in the described object that described preparation is distributed to (being preferably a non-proton image) is produced, it is characterized in that: described fluid adopts device according to the present invention to control, and described fluid is preferably controlled in the respiratory system of object.
Imaging process according to the inventive method can be undertaken by common process.
Wadding is controlled and is advantageously accounted for 2~100%, more preferably accounts for 5~30% in breathing stroke, can position in this any stage of breathing stroke.If the polar words of the gas of controlling then preferably are polarised to P=5% at least, preferably at least 10%.
The publication of for this reason quoting is used for referencial use here.
By accompanying drawing embodiments of the invention are described further below, in the accompanying drawing:
Fig. 1 is the sketch map that is placed in the flexible pipe a kind of gas wadding between two kinds of other air-flows;
Fig. 2 is the sketch map of applicator of the present invention;
Sketch map when Fig. 3 is in the running position for applicator shown in Figure 2 just is being defeated by target patient at this position air;
Sketch map when Fig. 4 is in the running position for applicator shown in Figure 2 is just carried gas wadding, for example hyperpolarization to target patient in this position 3He;
Fig. 5 is the sketch map of another kind of applicator, and it is similar to the situation of Fig. 3, but has the irrevocable formula valve of a passive driving, and this valve prevents that the air backflow from entering this applicator;
Fig. 6 is the sketch map of another applicator, and it is positioned at the running position the same with Fig. 4;
Fig. 7 illustrates in three similar breathings 3The He concentration curve;
Fig. 8 illustrates in four similar breathings 3The He concentration curve.
Fig. 2 represents to be used to control with 10 3The overall picture of the equipment mode of He wadding.The people 101 of examine lies in the magnetic field of nuclear magnetic resonance, NMR chromatographical X-ray video camera 102.His breathe air arrives applicator 20 by a flexible pipe 301, and it delivers air to the patient.The air of breathing out can reclaim by pipeline 302.
To controlled breathing, can under controlled condition, provide the suction air from respiratory organ 30; This also allows the density of regulating special-purpose oxygen in breathe air.Reclaim under the situation of special gas after plan is being breathed, they for example can be collected in the bag 303.
The special gas wadding is injected breathe air by applicator 20, this applicator is placed in the described nuclear magnetic resonance, NMR chromatographical X-ray video camera, near patient's head, the result who does like this can avoid other space, blind area the space, blind area in inevitable breathing hose.Hyperpolarization 3The reservoir 201-203 of He can regard the parts of applicator 20 here as.This gas is hyperpolarization externally, and is placed in the container 201, this container gassy in the time of in supplier or manufacturer's hands.This container 201 for example is made up of a glass unit that has valve 202, can be connected to applicator 20 by an adpting flange 203. 3He container 201 itself is allowed very long slack time, and every other and hyperpolarization 3The contacted surface of He should be less.When some special-purpose air were passed through, the time delay in respective volume was just shorter, and produced simultaneously polarization loss is just less.Why Here it is is placed in the comparatively ideal reason of described nuclear magnetic resonance, NMR chromatographical X-ray video camera internal ratio with applicator.In contrast, purge gas such as nitrogen for example can be introduced from external cylinder 210 by pipeline 211.Applicator 20 is controlled by a computer 220 itself, and it is connected with applicator 20 with control line 221 with the hydraulic pressure instrument by electric, pneumatic.
Fig. 3 is the sketch map of applicator 20.Parts in the zone of being drawn a circle to approve by chain-dotted line all are placed in the magnetic field of chromatographical X-ray video camera.Their material and size should preferably satisfy the requirement of illustrating previously.Especially, the transverse section of all transmission breathing gas all decision design have should be big relatively the cross sectional area district, be that the area of a circle district of 22mm is suitable for example promptly with diameter.This just makes and also is laminar flow during up to 560ml/s at flow.
Before notes were executed ideal gas wadding, the patient was air-breathing and exhale by pipeline 302 by pipeline 301/305, valve 240 and pipeline 241.Controlling described wadding constantly, promptly when a certain amount of gas 2 (Fig. 1) is introduced pipeline 241, normal airflow from pipeline 301 and 305 is blocked by valve 240, and what replace it is that the gas from should expansion type container 231 of certain volume is defeated by patient (referring to Fig. 4).These expansion type containers 231 are positioned at a housing 230.Employing is arranged in the conversion valve of dislocation (relatively and Fig. 3 valve 240 and be biased in the right side), and these expansion type containers are connected with pipeline 305.If applicator 20 is connected with a respiratory organ, so in this case, housing 230 bears the initial pressure from the breathe air of this respiratory organ.Consequently these expansion type containers 231 are pressed sky, are led the patient by the gases in pipeline 206, valve 240 and the pipeline 241 original injection expansion type containers 231.If these expansion type containers 231 empty (this raises by the pressure on the differential pressure transducer 244 and surveys), reset valve 240 so, the wiring of eupnea gas flows to patient (Fig. 3).Described differential pressure transducer 244 is connected by a passage 235 in pipeline 242 and the housing 230.
In the place that hyperpolarized gas obtains controlling, the air of exhalation preferably should not be back to applicator.When adopting a respiratory organ, it monitors air-breathing and expiration phase, and therefore allows gas freely by pipeline 301, or opens the valve (not shown) that is positioned at pipeline 302 ends.For this operational mode, pipeline 241 and 302 is connected to opening and annotates by an opening member that to execute gas just enough by a Y spare.
If adopt not with the applicator 20 of respiratory organ, the patient normally sucks air by pipeline 301 and 305, valve 240 and pipeline 241 so.Enter applicator 20 in order to prevent that air from refluxing, correspondingly adopt the valve 245 (Fig. 5) of a passive driving.When exhaling, this valve blocking-up pipeline 241 and clear hole pipeline 302.Under this operational mode, the patient inhales expansion type reservoir 231 empty after valve 240 conversions.In this case, the pressure differential on the differential pressure transducer also causes valve 240 revolutions.
Fig. 6 illustrates a kind of applicator, and it provides the valve 310 and 311 of passive driving on respiratory organ pipeline 301 and expiration pipeline 302.This point can adopt a Y spare to combine with these valves and realize, can avoid in this way causing that by all valves 245 as shown in Figure 5 of commodity valve the chance of hyperpolarized gas is lax.
For the respiratory of monitored patient, an effusion meter 304 is inserted air-breathing branch (pipeline 301,305).Expiration phase or by pipeline 211 from outside gas storage cylinder or from 3He case 201 is to 231 gas injections of expansion type reservoir.Valve 202 at adpting flange rear cabinet 201 just is opened.Gas injects by computer-controlled valve 212 and 204 is respectively originally pressed empty expansion type reservoir 231.Tolerance is determined according to the quantity that will annotate the wadding of executing.In the present embodiment, air-flow is regulated by metering valve 213 and 205 respectively, and Chuan Shu tolerance was for example injected expansion type reservoir 231 in about 0.5 second like this.The setting position of metering valve 205 determines that according to the initial pressure in pipeline 211 or the case 201 (relevant with atmospheric pressure) this initial pressure is generally 4 crust when adopting nitrogen, is adopting 3Be 2 to 0 crust during He, this depends on has stay in the case 201 for how much gas.
To reservoir 231 gas injections the time, air is discharged from housing 230, and flows away from effusion meter 232, and this effusion meter 232 is connected to passage 236 and valve 233 and is positioned at the pipeline 234 of release position in this stage.When expansion type reservoir 231 is filled with, note and also temporarily compile from the measurement data of effusion meter.The discharged air amount of Que Dinging is suitable with the tolerance of injecting expansion type reservoir 231 in this way.Thereby the tolerance of injecting expansion type reservoir 231 can determine indirectly that this is very favourable when especially considering the sensitivity when they contact with some material when handling polarized gas.As the function of this gas volume of surveying, the gas injection time is when being 0.5 second, but with the error of the mode injected gas volume of repeated authentication less than 5%.
In the time can determining according to known throughput in advance the switch time of valve, the temporary transient delay that causes because of the valve switch time can be compensated, and valve can be done sth. in advance known delaying and start.This means that especially the precision of controlling the wadding time can arrive within 20 milliseconds, and this can be limited in Δ q<500ml/s20ms with the uncertain amount that sucks tolerance in advance when supposing respiratory flow for 500ml/s, promptly less than 10ml.Be noted that in all cases gas must be inhaled in the blind area volume in the pipeline 241 between next comfortable valve 240 and the patient before waiting to annotate the wadding arrival patient who executes.Therefore advantageously applicator 20 directly is placed near patient's the head.The blind area volumes can resemble the 60ml little in the present embodiment in the pipeline 241 like this.
Employed valve, metering valve and effusion meter adopt conventional commercial parts as far as possible.In the present embodiment, valve 204 and 233 can move by fluid pressure type, is adapted to required size, can be made by the material of suitable selection.Valve 240 advantageously fluid pressure type drives, and advantageously design like this makes that at translate phase all entrance and exits are connected.This just guarantees that the air-flow that flows to the patient can not be blocked when controlled valve.
When transmitting by applicator 3Thermometrically has been carried out in the polarization loss of He.By the NMR method relaxation effect of the relevant parts of applicator is measured.The expansion type reservoir of being made by the He-airtight film is after purge falls oxygen remnants well with pure nitrogen gas, and be 20 to 40 minutes its slack time.Only be used for respiration because deposit into the gas of expansion type reservoir, and execute former seconds at notes at the most and inject, so polarization loss is less than 1%.Changed the slack time relevant with the position of measuring in valve 240 in 10 to 20 seconds, therefore when flowing through in 1 second, can keep more than 90% 3The He polarization.To the gas injection of expansion type reservoir the time, when gas flows through additional pipeline, can not produce tangible polarization loss.In a word, arrive the patient more than 90% original polarization.
Fig. 7 shows that how sharply and how to inject the wadding that produces with described applicator can be.Produce three similar breathing stroke (a) and (b) and (c), they have differently placing constantly of breathing stroke 3The He wadding is measured indirectly and is left in outlet (opening member) gas 3The content of He, method is: carbon dioxide is added in the respiratory organ air and adopt relevant conventional CO 2CO in the gas on the instrumentation amount opening member 2Amount.In three similar breathings 3He content is overlapping to be illustrated.
How Fig. 8 changes if illustrating wadding size (duration).Produce four similar breathing strokes (d), (e), (f) and (g), they 3The He wadding progressively becomes greatly, 3The content of He is determined as described in Figure 7.The same with Fig. 7, the result is overlapping to be illustrated.

Claims (14)

1. the device that convection cell is controlled comprises a variable-volume fluid reservoir and the mozzle from a fluid issuing of fluid reservoir guiding; A first fluid inlet and one second fluid intake; One first detector is used to survey the fluid stream between described conduit and described reservoir; One first valve, be used to allow or prevent fluid from described first the inlet flow to described reservoir by described conduit; One second valve, it is set the position first and allows that fluid flows to described outlet and prevents that fluid from flowing to described outlet from described reservoir by described conduit by described conduit from described second inlet, sets the position second and allows that fluid flows to described outlet by described conduit and prevents that fluid from flowing to described outlet from described second inlet by described conduit from described reservoir; One second detector is used to survey the fluid that flows in the described conduit from described second inlet and flows; With an activator, be used to control the operation of described first and second valves.
2. device according to claim 1, wherein said reservoir is a kind of container of flexibility, is placed in the inflexible container with a passage, described first detector is placed in there, surveys fluid stream by this passage.
3. according to each described device in claim 1 and 2, it also provides a valve, be used for fluid stream is introduced described conduit so that arrive one second outlet or one second reservoir and prevent that described fluid from flowing to and reach described variable-volume reservoir from described outlet.
4. according to the described device of above-mentioned each claim, it also comprises the gas source of described first inlet of receiving of a hyperpolarization.
5. according to the described device of above-mentioned each claim, it also comprises a respiratory organ of receiving described second inlet.
6. according to the described device of above-mentioned each claim, it also comprises one the 3rd inlet and one the 3rd valve, it allows that fluid flows to described variable-volume reservoir from described the 3rd inlet, and wherein said activator also is used to control the operation of described the 3rd valve.
7. according to the described device of above-mentioned each claim, the inner surface of wherein said variable-volume reservoir can be flow to described conduit by described first inlet with all and all be made by nonmagnetic substance with the surface that fluid contacted of flowing out described conduit by described outlet.
8. device according to claim 7, wherein said nonmagnetic substance is selected from glass, titanium and plastics.
9. according to the described device of above-mentioned each claim, wherein the structure of the described conduit between described second valve and described outlet can make the fluid stream that flows through wherein be essentially laminar flow.
10. according to the described device of above-mentioned each claim, it is made by nonmagnetic substance.
11. according to the described device of above-mentioned each claim, it has:
-one first inlet (203) is used to introduce first kind of vaporous material, especially a kind of gas that polarized atom (atomic nucleus) arranged;
-one metering device (230,231), it is connected with this first inlet (203), the volume of first kind of gaseous material that be employed is measured control;
-one second inlet (301,305) is used to introduce second kind of vaporous material;
-one measuring device (304) is used to measure the volume through second gaseous material of the second inlet introduction;
-one outlet (241,243) is used for first and second kinds of gaseous materials;
-one changeover valve (240), its end is connected with second inlet (301,305) with metering device (230,231), the other end is connected with outlet (241,243), can select to export (241,243) in the first valve setpoint position and be connected, can select to export (241,243) in the second valve setpoint position and be connected with metering device (230,231) with second inlet (301,305);
-metering device (230,231) has an expansion type container (231) that joins with first inlet, be placed in the housing (230), this housing provides at least one passage (235,236), another measuring device (232,244) is connected with this passage, measures at container to flow out the gas of housing (230) between (231) phase of expansion and/or flow to the gas of housing (230) during container (231) shrinks;
-one control unit (220), it is connected with changeover valve (240) with two measuring devices (304,232,244),
-as the function of amount of gas discharge from the housing (230) of metering device (230,231) and that measured by described another measuring device (232,244), first kind of gaseous material of this control unit control flows to the volume of the expansion type container (231) of metering device (230,231)
-as the function of second kind of gaseous material quantity being measured by first measuring device (304) or after the time of one section setting used up, this control unit was transformed into the second valve setpoint position with changeover valve (240) from the first valve setpoint position,
-as the function of the amount of gas in the housing of being measured by described another measuring device (232,244) (230) that flows to metering device (230,231), this control unit is transformed into the first valve setpoint position with changeover valve (240) from the second valve setpoint position.
12. according to each described device in the claim 1 to 10, it also comprises a computer control device.
13. magnetic resonance imagine method, wherein a kind of fluid MR preparation supplies to an object with the wadding form, the MR image of at least a portion in the described object that described preparation is distributed to is produced, and it is characterized in that: described fluid adopts and controls according to the described device of above-mentioned each claim.
14. method according to claim 13, wherein said MR preparation is 3The He-NMR preparation.
CN98811897.1A 1997-11-14 1998-11-13 Apparatus for fluid administration Pending CN1281345A (en)

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