WO1999053332A1 - Use of a hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs - Google Patents
Use of a hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs Download PDFInfo
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- WO1999053332A1 WO1999053332A1 PCT/GB1999/001095 GB9901095W WO9953332A1 WO 1999053332 A1 WO1999053332 A1 WO 1999053332A1 GB 9901095 W GB9901095 W GB 9901095W WO 9953332 A1 WO9953332 A1 WO 9953332A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
- G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
- G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
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- This invention relates to a method of magnetic resonance imaging of the human or animal (e.g. mammalian, reptilian or avian) body by which lung function and, if desired, morphology may be investigated.
- human or animal e.g. mammalian, reptilian or avian
- Lung function is of interest to physicians, especially when dealing with patients who may have abnormalities of ventilation or perfusion or other determinants of gas exchange in the lung.
- five conditions must be met: 1. gas (air) must flow into and out of the lungs;
- the gas must be distributed evenly within the lungs ;
- the distribution of the blood in the lungs should match the distribution of gas in the alveolar space (i.e. where the gas penetrates to, blood should flow).
- the perfusion agent is generally a particulate (e.g. 99m Tc-macroaggregated albumin) which is administered intravenously upstream of the lungs and lodges in the precapillary arterioles .
- a particulate e.g. 99m Tc-macroaggregated albumin
- Images are recorded with a gamma camera and the signal intensity may be used to detect local abnormalities in blood flow.
- the ventilation agent is generally a radioactive gas or aerosol or microparticulate, e.g. 133 Xe, 127 Xe or 81m Kr, or a 99m Tc-DTPA aerosol or 99m Tc-labelled carbon particles.
- the agent is inhaled and an image is recorded with a gamma camera. Signal intensity and distribution may be used to detect airway obstructions or regional abnormalities in ventilation.
- various different lung malfunctions, diseases or abnormalities may be diagnosed, e.g. pulmonary embolism, pleural effusion/atelectasis, pneumonia, tumour/hilar adenopathy, pulmonary artery obstruction, AVM, CHF, and intravenous drug use.
- Heterogenous perfusion patterns may likewise be used to diagnose various disease states or disorders, e.g. CHF, lymphangitic carcinomatosis, non-thrombogenic emboli, vasculitis, chronic interstitial lung disease, and primary pulmonary hypertension.
- Decreased perfusion to one lung may be used to diagnose pulmonary embolism, pulmonary agenesis, hypoplastic lung (pulmonary artery stenosis) , Swyer- James syndrome, pneumothorax, massive pleural effusion, tumour, pulmonary artery sarcoma and shunt procedures for congenital heart disease.
- VQ imaging however involves exposing the patient to radiation doses from two radiopharmaceuticals in two temporally separate imaging procedures. Clearance of the injected particulate agent is relatively slow and the agent is taken up in other organs besides the lungs. Moreover, in patients with severe pulmonary hypertension, the injected particulate causes a risk of - 3 - acute right heart failure. For pregnant patients the radiation dose involved in VQ imaging results in undesirable levels of radiation exposure for the foetus. Furthermore, for most diagnostic purposes mentioned above the resolution of conventional VQ imaging is unsatisfactory.
- the non-equilibrium spin state distribution is achieved by placing the subject in a strong magnetic field (to enhance the population difference between the proton spin states at equilibrium) and by exposing the subject to pulses of rf radiation at the proton Larmor frequency to excite spin state transitions and create a non-equilibrium spin state distribution.
- a strong magnetic field to enhance the population difference between the proton spin states at equilibrium
- pulses of rf radiation at the proton Larmor frequency to excite spin state transitions and create a non-equilibrium spin state distribution.
- the maximum deviation from equilibrium is that achievable by spin state population inversion and, since the energy level difference between ground and excited states is small at the temperatures and magnetic field strengths accessible, the signal strength is inherently weak.
- hyperpolarize i.e. obtain a nuclear spin state population difference greater than the equilibrium population difference
- an imaging agent containing nonzero nuclear spin nuclei e.g. by optical pumping, by polarization transfer or by subjecting such nuclei ex vivo to much higher magnetic fields than those used in the mr imaging apparatus
- the hyperpolarized agent is conveniently in gaseous form, e.g. 3 He or 129 Xe, and it may thereby be administered by inhalation into the lung and the mr signal detected may be used to generate a morphological image of the lungs .
- the relaxation time T for 3 He in the lungs is about 10 seconds it is feasible, using fast imaging techniques, to generate a morphological image of the lungs from the 3 He signal following inhalation of hyperpolarized 3 He gas and at any desired stage of the breathing cycle, e.g. during breathhold. Since the mr signal selected is from the 3 He atoms and since the helium is in the gas phase in the lungs, the image detected is essentially only of the airways into and within the lungs.
- the hyperpolarized agent as a bolus followed or preceded by other gases or aerosols, e.g.
- the hyperpolarized agent can be positioned at any desired section of the airways or other aerated spaces in the body, e.g. it may be flushed from the trachiobronchial tree and the image generated is then essentially only of the alveolar space .
- functional imaging of the lungs may be carried out effectively using mr imaging of an inhaled hyperpolarized agent by making use of the variation with time of the relaxation rate Tj_ of the hyperpolarized agent in conjunction with imaging of the regional and temporal distribution of ventilation using hyperpolarized gases.
- the invention provides a method of detecting regional variations in oxygen uptake from the lungs of an air-breathing animal subject, e.g. a mammalian (human or non-human) , avian or reptilian subject, said method comprising administering into the lungs of said subject a diagnostically effective amount of a gaseous hyperpolarized magnetic resonance imaging agent, detecting the magnetic resonance signal from said agent in said lungs, determining the temporal variation in relaxation rate (e.g.
- Tj_ relaxation rate for said signal for at least one region of interest within said lungs, and from said variation generating a qualitative or quantitative value or image indicative of the oxygen concentration in the alveolar space in said at least one region of interest, and if desired the time dependency of such concentration as a result for example of physiological process, e.g. oxygen uptake by perfusion.
- the method of the invention also involves generation of a temporal and/or spatial image of the distribution of the hyperpolarized agent in at least part of the lungs of the subject, preferably in the alveolar space within the lungs.
- the method also involves generation of a magnetic resonance image of at least part of the lungs of the subject following administration into the subject's vasculature of a second mr agent, preferably an agent which affects proton relaxation (with the image generated being a proton mr image) or more preferably an agent containing non-proton mr active nuclei (e.g. 19 F, 13 C, 31 P, 17 0, etc.) in which case the mr image will be generated from mr signals from such non-proton mr active nuclei.
- the mr active nuclei in the second agent will preferably not be the same as those in the hyperpolarized agent unless the image generated using the second agent is generated at a time when the lungs contain substantially none of the hyperpolarized agent.
- Lung volume may also be estimated from the integrated 3 He mr signal (or by 3 He mrs) following inhalation of the 3 He without air, breathhold, and expiration where the expired volume is measured directly and the residual hyperpolarization of the retained 3 He is extrapolated from the hyperpolarization value (signal strength) monitored during breathhold.
- the method of the invention it is preferred that for at least part of the mr signal detection period (preferably at least 1 second, more preferably at least 5 seconds, still more preferably at least 10 seconds, e.g. 20 sec to 1 minute), there be substantially no flow of gas into or out of the lungs, e.g. that there should be a breathhold period, and that the indication of oxygen uptake be derived from mr signals detected during at least part of this period.
- the method of the invention will also involve mr signal detection during gas flow into and/or out of the lungs with or without a period of breathhold. In this way, spatial or temporal images or other indications of lung ventilation may be generated from the detected mr signals.
- the detected mr signal derives from the hyperpolarized agent, the signal strength is effectively independent of the primary field strength of the magnet in the mr imager. Accordingly low or high field, e.g. 0.05 to 3.5T, machines may be used.
- Figures la and lb show 3 He mr images showing the effect of oxygen and flip angle on the images obtained using a 40 mL bolus of 3 He;
- Figure 2 shows 3 He mr images of the airway
- Figure 3 shows the 3 He mr signal strength in the trachea during inspiration and breathhold where a bolus of 3 He is estimated
- - 7 -
- Figure 4 shows a plot of regional F ⁇ p 0 2 against F et 0 2 (see Example 7) ;
- Figure 5 showe a plot of F ⁇ p 0 2 versus time (see Example 7) ;
- Figure 6 shows a plot of D n against number of images
- Figure 7 shows a plot of signal intensity evolution (see Example 3) ;
- Figure 8 shows a plot of signal against number of images (see Example 3) ;
- Figure 9 shows a plot of signal intensities as a function of time (see Example 5) ;
- Figure 10 shows a plot of p0 2 versus time (see Example 6) ;
- Figure 11 shows images from a healthy volunteer after inspiration of a single bolus (see Example 9) ;
- Figure 12 shows a plot of signal versus time (see Example 9) .
- the method of the invention involves administration of a gaseous hyperpolarized mr agent.
- a gaseous agent is meant a gas as such (e.g. 3 He or 129 Xe) or a particulate agent held in the gas phase, e.g. an aerosol of powder or droplets.
- the gaseous carrier preferably is substantially free of paramagnetic gases such as oxygen.
- the hyperpolarized agent will conveniently have a polarization degree P of 2 to 75%, e.g. 10 to 50%.
- the mr active (i.e. non-zero nuclear spin) nuclei which are hyperpolarized may be any mr active nuclei which can be hyperpolarized and which can be presented in a gaseous form (i.e.
- nuclei elemental or molecular form, e.g. SF 6 ) which is physiologically tolerable.
- appropriate nuclei include various noble gas, carbon, nitrogen and fluorine isotopes; however the noble gases, e.g. He and Xe, and most especially 3 He , are the most preferred. Accordingly, the discussion below will present the invention in terms of 3 He-mr imaging although it does as indicated above, extend to cover the use of other mr active nuclei.
- oxygen transport within the functional units of the lung i.e. the alveolocapillary unit is characterized by a relationship governed by mass conservation :
- the net amount of oxygen entering the alveolocapillary unit by the airways has to be equal to the net amount of oxygen leaving the alveolocapillary unit on the blood side. This may be expressed by the equation:
- I 0 2 fractional inspiratory concentration of oxygen
- F E 0 2 fractional expiratory concentration of oxygen
- c a 0 2 oxygen content of arterial blood
- c v 0 2 oxygen content of mixed venous blood
- Equation (1) provides the following equation for the ventilation-perfusion ratio V'/Q:
- VI c 3 0 - C..O-, (2) Q F x 0 2 - F E 0 2
- Oxygen contents as well as fractional oxygen concentrations can both be written as functions of oxygen partial pressure, yielding the following equation:
- V_L k_p E 0 2 - p v 0 2 l + f(p a 0 2 - p v 0 2 ) (4)
- Both k and f depend on a variety of factors, e.g. on barometric pressure, the solubility constant of oxygen in plasma, the dissociation curve of oxygenated haemoglobin, etc., all of which are known.
- the method may be used to measure regional ventilation, regional partial pressure of oxygen and its time course, with high spatial and temporal resolution.
- Regional oxygen partial pressure may be measured by hyperpolarized gas magnetic resonance imaging, e.g. hyperpolarised 3 He gas magnetic resonance imaging.
- hyperpolarized gas magnetic resonance imaging e.g. hyperpolarised 3 He gas magnetic resonance imaging.
- ultrafast MRI sequences are preferably used allowing sequential measurements of the 3 He signal, and its decay, which is dependent both on oxygen and MR acquisition (see Figures 1 a and b) .
- Signal decay induced by the MR sequence is corrected for by variation of the flip angle and/or of the inter-scan delay.
- Oxygen concentration inspired into the alveolocapillary unit is not constant during a single inspiration, due to the contribution of deadspace . Therefore, mean inspiratory concentration may be calculated based upon determination of deadspace (from airway imaging by 3 He; see Figure 2) , and from the inspiratory concentration administered at the mouth. - 10 -
- Regional ventilation may be measured by quantitative analysis of temporal changes in hyperpolarization signal in the trachea, and parallel to this, in the alveolar space, following inspiration of a single bolus of hyperpolarized gas. This analysis is performed on the basis of a mass balance, which allows the determination of functional residual capacity and serial deadspace on a global and regional basis. These signal changes can be measured over several respiratory cycles by ultrafast pulse sequences (e.g., temporal resolution ⁇ 150 ms) and flow flip angles (Fig. 2 and 3) .
- ultrafast pulse sequences e.g., temporal resolution ⁇ 150 ms
- flow flip angles Fig. 2 and 3
- the preferred MRI sequences for use in the method of the invention are: for oxygen partial pressure determination, short repetition time gradient-recalled echo sequences with small flip angle; and - for determination of ventilation, ultra-short repetition time ( ⁇ 2 ms) gradient-recalled echo sequences with small flip angle, or echo-planar pulse sequences, or ultra-fast sequences using low flip angle and free induction decay.
- n the number of image acquisition
- r the number of radiofrequency impulses (lines) per image acquired
- a the flip angle imposed by each consecutive radiofrequency impulse upon the nuclear spin polarization of 3 He in the acquisition volume.
- signal intensity (S n ) also begins to decay according to an exponential function, to arrive (within a given time interval Dt) at S n+1 :
- the time constant of this decay is determined by the longitudinal spin relaxation time of 3 He, T l r which is shortened in the presence of paramagnetic molecular oxygen .
- A384 : 444-450 (1997) describe apparatus which can be used to produce 3 He with a polarization degree P of at least 50% at a flow of 3.5 xlO 18 atoms/sec. or 40% at a flow rate of 8xl0 18 atoms/sec.
- the hyperpolarized gas may then be filled into glass cylinders, e.g. made of glass which has a low iron content and no coating. These cylinders can be closed by a stop-cock and transported to the mr imaging site, preferably within a magnet, eg a 0.3mT magnet. Under such conditions, the 3 He has a relaxation time (T x ) of up to 70 hours.
- the hyperpolarized gas is preferably administered in a bolus into an application unit through which the subject under study may breath freely or alternatively ventilation may be supported by artificial ventilation.
- artificial ventilation apparatus will preferably be used and the animals will preferably be anaesthetized and relaxed.
- free breathing through the ventilation unit will generally be preferred.
- the 3 He bolus conveniently of 1 to 1000ml, may be administered at a desired point within the breathing cycle, generally at or close to the beginning of inspiration.
- the bolus - 13 - size used will depend on the lung size or tidal respiration volume of the subject and will thus vary with subject size or species. However a bolus of 2 to 50%, preferably 5 to 25%, of tidal respiration volume may be suitable.
- the 3 He bolus passes into the airways within about one second with alveolar filling occurring rapidly thereafter for healthy/unobstructed tissue. If inspiration is followed by a period (e.g. of 1 to 60 seconds during which there is substantially no gas flow into or out of the lungs, e.g. a period of breathhold) , the 3 He-mr signal gradually decays at a relaxation rate of the order of 10 seconds. The relaxation rate however is not constant spatially or temporally. Three significant factors contribute to this: loss of polarization due to the magnetic field changes required for mr imaging; loss of polarization due to relaxation enhancement by gaseous oxygen present in the lungs ; and loss of polarization due to relaxation enhancement by the tissue/gas boundary.
- the first and third of these factors are constant during a period of no gas flow to/from the lungs; however, 3 He filled volumes as well as oxygen concentration will vary due to physiological processes, e.g. as oxygen is taken up from the lungs in the alveolar space. As a result, in a region of interest where oxygen concentration drops the 3 He relaxation time will increase with time even though absolute signal intensity will continue to drop.
- relaxation rate enhancement by lung tissue plays a subordinate role in terms of the overall contributions to the 3 He relaxation rate, it does have a non-uniform effect as different tissues or abnormalities have different effects on the relaxation rate. It is thus preferred not to estimate the oxygen contribution to the relaxation rate by simple reference to a phantom - 14 - undergoing the same field gradient changes as the subject's lung. Use of a phantom is similarly non- preferred due to the inhomogeneity in the applied field across the volume in which the 3 He distributes. Accordingly it is preferred to extract the oxygen contribution to the relaxation rate by mr signal detection during at least two different types of signal generation, e.g. with the different sequences being interleaved. Thus for example the different sequences may involve different RF excitation intensities and/or different sequence intervals ( ⁇ ).
- the magnetic field change contribution to the relaxation is desirably minimized so as to prolong the period over which a signal with an acceptable signal to noise ratio can be detected.
- This is generally achieved by using small flip angles (e.g. less than 7°, preferably less than 4°) in the imaging sequences and in this way mr signals may be detected for up to 60 seconds following bolus 3 He administration.
- small flip angles e.g. less than 7°, preferably less than 4°
- mr signals may be detected for up to 60 seconds following bolus 3 He administration.
- rapid image generating techniques e.g. fast gradient echo techniques or other techniques with an image acquisition time of less than 2 seconds, preferably 1 second or less.
- images generated in this way may have a spatial resolution (i.e. voxel size) of less than 20 mm 2 , which is far superior to the scintigraphic ventilation images in conventional VQ imaging.
- the regions of interest studied in the method of the invention will generally be the alveolar space and thus it is generally preferable that the 3 He bolus be followed in the same gas intake by air or nitrogen to flush the 3 He from the tracheobronchial tree and into the alveolar space. - 15 -
- the method of the invention may, and probably will, involve generation of ventilation images, showing spatial and/or temporal distribution of 3 He, thereby permitting ventilation and perfusion to be determined in the same imaging procedure (unlike VQ imaging) .
- ventilation images may identify airway obstructions simply by identifying regions to which the J He does not penetrate, penetrates slowly, or penetrates at lower than normal concentrations.
- Obstructions and associated hypoperfusion, normal perfusion or hyperperfusion can also be identified by following the time dependence of the 3 He relaxation rate for slowly penetrated alveolar space as the oxygen concentration in such areas may be abnormally low or high.
- the local relaxation rate may be or become abnormally high or low.
- 3 He mr imaging may be combined with perfusion imaging with or without administration of a contrast agent, using a second imaging agent administered into the vasculature, e.g. a blood pool agent such as a polymeric paramagnetic chelate, or a superparamagnetic agent or, more preferably because of its oxygen sensitivity, a 19 F fluorocarbon emulsion.
- a blood pool agent such as a polymeric paramagnetic chelate, or a superparamagnetic agent or, more preferably because of its oxygen sensitivity, a 19 F fluorocarbon emulsion.
- imaging would be proton mr imaging, in the latter case 19 F mr imaging.
- the perfusion data collected in this way is not absolutely equivalent to that generated in the method of the invention since the second imaging agent distribution merely identifies the - 16 - regions of the lung to which blood flows and not whether or not oxygen uptake by the blood occurs in such regions. Accordingly, the perfusion data from the method of the invention provides a more comprehensive portrayal of lung function.
- the method of the invention may be used as part of a method of diagnosis of lung malfunction, disease, etc. or indeed in combination with a method of treatment to combat, i.e. prevent or cure or ameliorate, a lung malfunction or disease, etc., e.g. a method involving surgery or administration of therapeutic agents or a method of diagnosis of one of the lung malfunctions or diseases mentioned above.
- a method of treatment to combat, i.e. prevent or cure or ameliorate, a lung malfunction or disease, etc.
- Such methods form further aspects of the present invention as does the use of 3 He (or other mr active nuclei containing materials) for the preparation of a hyperpolarized imaging agent for use in methods of treatment or diagnosis involving performance of the method of the invention.
- the objectives in this Example were to realize single-breath, single-bolus visualization of intrapulmonarily administered 3 He to analyse nuclear spin relaxation of 3 He in vivo and to determine the regional oxygen concentration, i.e. [0 2 ] , and its time dependent change by perfusion.
- a double acquisition technique is described which also permits estimation of regional gas transport .
- the source of the MR signal is the large non-equilibrium polarization of 3 He .
- This polarization is achieved by means of direct optical pumping from its metastable state ls2s 3 S 1 at lmb with - 17 - subsequent compression to a convenient pressure of 1-6 bar.
- the apparatus is described by Surkau et al . Nuc . Instr. & Meth. A 384 (1997) 444-450 and is capable of yielding P > 50% at flow of 3.5 x 10 18 atoms/s and 40% at flow 8 x 10 18 atoms/s.
- the gas is filled into glass cylinders with long relaxation times. Cylinders for medical application are made from "Supremax glass" with low iron content and no coating.
- Relaxation of the non-equilibrium polarization of inhaled 3 He in vivo is mainly caused by NMR excitations and the presence of oxygen. Relaxation by lung tissue plays a subordinate role as shown by experiments below.
- the time evolution of the polarization P inside a two- dimensional partition inside ventilated lung spaces can be described by rate equations . Considering the flip angle ⁇ and the partial oxygen pressure po we define a time-averaged relaxation rate by NMR via the equation
- Y' may be neglected if V ⁇ V .
- the second set of images is acquired retaining ⁇ , but doubling . Assuming p 02 and its time development to be equal in a given ROI during both series, the E n values of corresponding images can be subtracted giving
- Method 2 The second set of images is acquired with the same - 20 -
- Wall relaxation by lung tissue is negligible.
- the effect of wall relaxation was measured in a deoxygenized lung of a dead pig by double acquisition sampling with varied flip angles (method 1) .
- oxygen was washed out by ventilating with pure nitrogen for about 15 mins .
- Partition thickness was 120 mm in coronal orientation in order to excite 3 He spins in the entire lung volume.
- InterScan time ⁇ was 7 sees.
- a ROI of 415 pixel (6.5 cm 2 ) within the cranial left lung was examined.
- Figure 6 shows a linear graph (N total number of images taken, n the considered image number) .
- Solving equation (17) one determines the flip ⁇ 3.4°. Knowing this value, one can fit the signal intensity evolution with the image number given in Figure 7.
- p(t) p 0 - mt with time t, coefficient m and pressure p 0 at the beginning of the measurement.
- the oxygen density p 02 (t) is determined from the sequence of normalised logarithmic intensities E lf E 2 ...E n . The procedure is simplified if it is assumed a priori that the time dependence of p 02 be linear
- the time course of p 02 (t n ) was obtained via eq. [20] within a ROI in the middle section of the right lung which comprises 89 pixel and covers an area of 1.39 cm 2 . A linear decrease of p 02 with time was observed, thus confirming the assumption a posteriori.
- the dynamics of intrapulmonary 3 He polarization are changed significantly when diffusive and/or convective gas transport is taken into account . This is necessarily the case when the imaged partition is thin compared to the total lung volume.
- the inspiratory oxygen concentration was set to (30+1)%.
- Two series of nine images each were acquired with RF amplitudes of 10 and 20 V respectively.
- InterScan delays ⁇ were alternating 1.2s and 1.8s.
- the imaged object was a rubber bag of volume 0.5 liters.
- Parameter variation was realized with one single imaging sequence, permitting quantification of flip angle and oxygen concentration.
- Hyperpolarized 3 Helium 3 He is described as non- radioactive inhalational contrast agent for magnetic resonance (MR) tomography of ventilated lung spaces.
- MR magnetic resonance
- 3 He-MRI signal intensity is destroyed irrecoverably by (1) the presence of paramagnetic oxygen in the respiratory gas and (2) MR image acquisition itself.
- Regional intrapulmonary [0 2 ] as a sum of inspiratory oxygen concentration (FjOg) , distribution of ventilation, and oxygen uptake is determined in clinical practice globally over the whole lung. The aim was to use the effect of oxygen upon 3 He to visualise regional intrapulmonary [0 2 ] in MR for the first time on a regional basis.
- Interventions included variation of 3 He bolus sizes, of RF amplitudes for MR-image acquisition (10V and 20V) , of end-tidal [0 2 ] (0.16, 0.25, 0.35 and 0.45), and comparison of intrapulmonary [0 2 ] before and after induction of cardiac arrest.
- Figure 5 shows the analysis of the time course of oxygen concentration in the lung of a male volunteer, analysed with the double acquisition method with variation of flip angle as described in the present example above.
- Initial oxygen concentration at the beginning of the breathhold (0.189) and calculated oxygen decrease during apnea (0.01/s) can be followed.
- He gas was hyperpolarized to approximately 40-50% by optical pumping. 12 volunteers and 10 pneurologic patients inhaled such gas from glass cylinders of 300 mL volume and 3 bar pressure.
- 3 He-MRI was performed during breathhold using a 3D gradient-recalled-echo imaging sequence on a Siemens 1.5T clinical scanner, adjusted to have a transmitter frequency of 48.4 MHz and using a Helmholtz transmit/receive RF coil. A flip angle less than 5° was used.
- a series of 160 projection images was obtained with 128ms temporal resolution. Imaging was performed before, during and after application of a single bolus of approximately 300ml 3 He in five healthy volunteers (spontaneous breathing) .
- the signal intensities were corrected for depolarisation by RF excitation on the basis of equation (5) of this invention.
- Figure 11 Images from a healthy volunteer at time 0s, 0.13s, 0.26s, 0.65s, 1.17s, 1.95s, 3.77s and 6.37s after inspiration of a single bolus (285 mL) hyperpolarized Helium-3 are shown in Figure 11.
- Figure 12 shows signal-time- curves in trachea and in parenchyma on the right side of the lung in the patient of Figure 11. Shaded areas denote intervals of expiration (determined from the diaphragm position) , interrupted by intervals of inspiration (not shaded) .
- 3He signal appears in the trachea. It reappears during the expiratory cycles. After a delayed signal increase in alveolar space, 3He signal decreases - 31 - there due to T x relaxation, depolarisation by RF pulses, and due to expiration and inspiration with air.
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Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU34325/99A AU760339B2 (en) | 1998-04-09 | 1999-04-09 | Use of a hyperpolarized gas for MRI detection of regional variations in oxygen uptake from the lungs |
HU0300952A HUP0300952A2 (en) | 1998-04-09 | 1999-04-09 | Use of a hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
PL343379A PL192056B1 (en) | 1998-04-09 | 1999-04-09 | Method for detecting regional changes in oxygen capture from lungs and application of 3he or other material containing active nucleus in mr |
IL13894299A IL138942A0 (en) | 1998-04-09 | 1999-04-09 | Use of hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
JP2000543843A JP2002511329A (en) | 1998-04-09 | 1999-04-09 | Use of hyperpolarized gas for MRI detection of regional changes in oxygen absorption from the lung |
NZ507434A NZ507434A (en) | 1998-04-09 | 1999-04-09 | Use of hyperpolarized gas for magnetic resonance detection of regional variations in oxygen uptake from the lungs |
IL15560799A IL155607A0 (en) | 1998-04-09 | 1999-04-09 | Use of hyperpolarized gas for mri estimation of lung volume |
EP99915902A EP1070261A1 (en) | 1998-04-09 | 1999-04-09 | Use of a hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
CA002327733A CA2327733C (en) | 1998-04-09 | 1999-04-09 | Use of a hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
NO20005075A NO20005075L (en) | 1998-04-09 | 2000-10-09 | Use of a hyperpolarized gas for MRI detection of regional variations in oxygen uptake from the lungs |
IL138942A IL138942A (en) | 1998-04-09 | 2000-10-10 | Use of hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
IL155607A IL155607A (en) | 1998-04-09 | 2003-04-28 | Use of hyperpolarized gas for mri detection of regional variations in oxygen uptake from the lungs |
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GBGB9807879.3A GB9807879D0 (en) | 1998-04-09 | 1998-04-09 | Magnetic resonance imaging method |
GB9807879.3 | 1998-04-09 | ||
US09/057,979 US6370415B1 (en) | 1998-04-10 | 1998-04-10 | Magnetic resonance imaging method |
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Cited By (6)
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US6284222B1 (en) | 1998-11-03 | 2001-09-04 | Medi--Physics, Inc. | Hyperpolarized helium-3 microbubble gas entrapment methods |
WO2001074247A2 (en) * | 2000-04-03 | 2001-10-11 | Iep Pharmaceutical Devices Inc. | Method for measuring changes in the airways of humans and other mammals |
US6630126B2 (en) | 2000-03-13 | 2003-10-07 | Medi-Physics, Inc. | Diagnostic procedures using direct injection of gaseous hyperpolarized 129Xe and associated systems and products |
US6696040B2 (en) | 2000-07-13 | 2004-02-24 | Medi-Physics, Inc. | Diagnostic procedures using 129Xe spectroscopy characteristic chemical shift to detect pathology in vivo |
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