• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    METHOD AND APPARATUS FOR DETERMINING A CONSTRUCTION MEASUREMENT IN A VESSEL TRANSPORTING A FLUID MEDIUM A method and apparatus for determining a measurement of a constriction, such as a stenosis in a target region in a vessel transporting a fluid medium, such as the system human or animal coronary artery. A succession of pressure measurements and a corresponding succession of speed measurements are obtained at least at one location in the target region. The velocity of wave c in the fluid medium is determined as a function of the square of a change in pressure dP divided by the square of the corresponding change in velocity dU. The pressure changes of dP + feeds are separated from the back pressure changes dP- and an indicative measure of constriction is obtained using at least the separate feed pressure change.
    公开号:BR112012022685B1
    申请号:R112012022685-1
    申请日:2011-03-10
    公开日:2021-02-09
    发明作者:Justin Davies；Jamil Mayet
    申请人:Imperial Innovations Limited；
    IPC主号:
    专利说明:

    [001] The present invention relates to methods and mechanisms for determining the extent of a localized restriction for fluid to flow in a vessel, such as a pipe or tube. The invention had particular, though not exclusive, application in the measurement of a stenosis in a blood vessel and is particularly useful in determining the magnitude of a coronary stenosis in the human or animal coronary system.
    [002] Fractional flow reserve (FFR) is a technique widely applied in the coronary catheter laboratory in estimating coronary stenosis and the adequacy of stent placement. FFR is defined as the pressure behind (or distal to) a stenosis in relation to the pressure in front of (or proximal to) a stenosis. The result is a reason, that is, an absolute number. An FFR ratio of 0.5 indicates that a given stenosis results in a 50% drop in blood pressure through stenosis. More generally, an FFR indicates the ratio of a maximum flow of fluid together with a vessel in the presence of a restriction or constriction in the vessel compared to the maximum flow that should occur in the absence of that restriction or constriction.
    [003] The use of FFR has increased rapidly in the past few years when studies have demonstrated the limitations of visual estimation of strictures and the harm that can arise from inadequate angioplasty. This is conventionally accomplished by measuring the average drop in pressure on the side of a coronary stenosis under the condition of maximum hyperemia. However, under certain circumstances, for example, following an acute myocardial infarction, this can become unsafe. This can lead to inappropriate clinical decisions.
    [004] Since the pressure in most vascular beds increases from a single entry (ie, the aortic end of the vessel), pressure in the coronary artery increases both in the proximal (aortic end) and distal (microcirculatory end) contributions contributions in approximately equal proportions. Distal pressure is determined by 2 factors: (1) intrinsic (or 'passive') resistance through self-regulation of coronary microcirculation (2) extrinsic (or 'active') resistance through compression of small microcirculatory vessels that pass through of the myocardium.
    [005] The current FFR estimate attempts to reduce this distal pressure as much as possible by administering vasodilators, such as adenosine to achieve ‘maximal’ hypoeremia. However, while the administration of vasodilators will reduce passive mucrocirculatory resistance, it cannot suppress the microcirculatory pressure of distal origin that increases with the compression of the small vessels that pass through the contracting myocardium.
    [006] In this way, a small inaccuracy in FFR is inherent when it is not possible to eliminate the active resistance component. In addition, FFR can become inaccurate under pathological processes when the regulation of intrinsic or extrinsic resistance is affected. Examples of passive resistance dysfunction include diabetes mellitus, acute coronary syndrome, post myocardial infarction and hibernating myocardium. Examples of active resistant dysfunction include when an artery implies a hypokinetic or akinetic segment.
    [007] There is much published literature detailing such errors, which may explain why the close relationship between intravascular ultrasound (IVUS) and FFR in the highly regulated research laboratory is often not supported in the clinical setting.
    [008] It is an object of the present invention to provide an improved and / or alternative method and mechanism for measuring the extent of a localized restriction for fluid to flow into a vessel such as a pipe or tube. It is a further object of the invention to provide such a method and mechanism for use in measuring a stenosis in a blood vessel and, particularly, though not exclusively, in determining the magnitude or effects of a coronary stenosis in the human or animal coronary system.
    [009] According to one aspect, the present invention provides a method for determining a measurement of constriction in a vessel carrying a fluid medium, the method comprising the steps of: a) taking a succession of the first pressure measurements P1 and a succession of first velocity measurements corresponding to U1 at a first location within the vessel, the first location being within a first side of a target region; b) taking a succession of second pressure measurements P2 and a succession of corresponding second speed measurements U2 at a second location within the vessel, the second location being on a second side of the target region; c) for each location, determine the speed of wave c in the fluid medium as a function of the square of a change in pressure dP divided by the square of the corresponding change in speed dU; d) for the first location, determine an advance pressure change dP1 + as a function of the sum of the change in pressure dP1 and the change in speed dU1; e) for the second location, determine an advance pressure change dP2 + as a function of the sum of the change in pressure dP2 and the change in speed dU2; f) determine a separate advance flow reserve indicative of pressure drop across the target region as a function of the ratio of dP2 + / dP1 +.
    [010] The first side of the region can also be upstream of the target region and the second side can be downstream of the target region. The wave velocity can be determined at each location according to the equation c = (1 / p) □ (∑dP2 / ∑dU2), where p is the specific density of the fluid medium in the vessel. Steps d) and e) can comprise the determination of pressure changes of advances dP1 + and dP2 + according to the equations: dPi + = (pdPi + pcdUi) / 2 and dP2 + = (pdP2 + pcdUi) / 2. Step f) can include the integration or sum of multiple values of dP1 + and dP2 + to obtain pressure values of advances P1 + and P2 + and determining the separate advance flow reserve as a function of the ratio P2 + / P1 +. The method can be applied to a vessel in which there is a source of buoyancy pressure on either side of the target region, such as a vessel in the human or animal cardiac circulatory system. The succession of the first and second pressure measurements and the succession of the first and second velocity measurements can be obtained in at least one complete cardiac cycle of the human or animal body. The corresponding pressure and speed measurements can also be obtained simultaneously.
    [011] The present invention also provides a mechanism for determining a constriction pressure in a vessel carrying a fluid medium, the mechanism comprising: i) a pressure sensor and a speed sensor to obtain a succession of pressure measurements and velocity in the vessel at least one first location upstream of a target region and a second location downstream of the target region; ii) a processing module adapted to: receive a succession of the first pressure measurements P1 and a succession of corresponding first speed measurements U1 obtained at the first location within the vessel; receiving a succession of second pressure measurements P2 and a succession of corresponding second speed measurements U2 obtained at the second location within the vessel; for each location, determine the speed of wave c in the fluid medium as a function of the square of a change in pressure dP divided by the square of the corresponding change in speed dU; for the first location, determine an advance pressure change dP1 + as a function of the sum of the change in pressure dP1 and the change in speed dU1; e For the second location, determine an advance pressure change dP2 + as a function of the sum of the change in pressure dP2 and the change in speed dU2; and determining a separate advance flow reserve indicative of pressure drop across the target region as a function of the ratio of dP2 + / dP1 +.
    [012] The processing module can be adapted to determine the speed of wave c at each location according to the equation c = (1 / p) □ (∑dP2 / ∑dU2), where p is the specific density of the fluid medium in the pot. The processing module can still be adapted to determine said advanced pressure changes dP1 + and dP2 + according to the equations: dP1 + = (pdP1 + pcdU1) / 2 and dP2 + = (pdP2 + pcdU2) / 2. The processing module is still it can be adapted to integrate or add the multiple values of dP1 + and dP2 + to obtain pressure values of advances P1 + and P2 + and to determine the separate flow reserve of advance as a function of the ratio P2 + / P1 +. The mechanism may include means for monitoring a heart rate and for controlling said pressure sensor and said speed sensor to collect said succession of pressure measurements in said succession of speed measurements during a complete cardiac cycle.
    [013] The embodiments of the present invention will now be described by way of example and with reference to the accompanying drawings in which:
    [014] Figure 1 shows a schematic diagram of a vessel that carries a fluid medium in which the vessel has a constriction that causes a pressure drop;
    [015] Figure 2 shows a flow diagram of an advance pressure flow reserve measurement technique suitable for the analysis of a stenosis or other flow restriction in a vessel;
    [016] Figure 3 shows a schematic diagram of suitable mechanisms for the implementation of the method of figure 2;
    [017] Figure 4 illustrates the differences in the ratio between waves of proximal origin and waves of distal origin in a normal ventricle and in a severely hypokinetic ventricle;
    [018] Figure 5 is a schematic illustration of the drop in fractional flow reserve with increased coronary stenosis in normal or hypothesized impaired left ventricular function showing that in normal contraction VL, fractional flow reserve falls with increasing stenosis coronary (solid line), since in the hypothetical left ventricular model (dotted line), the fractional flow reserve falls by a very small amount and
    [019] Figure 6 shows a series of graphs that illustrate the separation of the total measured pressure in its components that go back and forth, as a function of time.
    [020] Recently, it has been described how it is possible to separate the aortic and microcirculatory components of a pressure wave within the coronary artery. See J E Davies ET AL: Evidence of a dominant backward-propagating “suction” wave responsible for diastolic coronary filling in humans, attenuated in left ventricular hypertrophy; Circulation 2006 April 11; 113 (14): 1768-78 and J E Davies ET AL: Use of simultaneous pressure and velocity measures to estimate arterial wave speed at a single site in humans; Am J Physiol Heart Circ Physiol 2006 February; 290 (2): H878-H885.
    [021] The present inventors have recognized that it is possible to estimate the severity of a stenosis, without the need to rely on (or remove) the distal procedure component, using an advance flow reserve technique described here. The advance pressure flow reserve overcomes limitations in conventional FFR by separating the proximal and distal components (or ‘advances’ and ‘delayed’) from the pressure waveform. The back pressure component can be removed. The estimate of coronary stenosis is simplified, making it very similar to the estimation of aortic stenosis when there is a simple pressure source (that is, the left ventricle).
    [022] The separation of coronary pressure has several advantages. First, it does not require the administration of adenosine to vasodilate the coronary microcirculation. Second, it is probably independent of left ventricular function making it applicable in acute coronary syndromes, post-myocardial infarction and hibernating myocardium, where conventional FFR is contraindicated as an estimation technique.
    [023] In practical terms, the separate pressure can be determined by measuring simultaneous pressure (P) and flow velocity (U) and calculating the pressure originating at the forward end (for example, aortic), P +, (Equation 1) and the pressure that originates from the delayed end (for example, microcirculator), P- (Equation 2). P + = ∑ (1/2) (dP + pcdU) (Equation 1) P- = ∑ (1/2) (dP - pcdU) (Equation 2)
    [024] dP represents a measured pressure change; dU represents a measured speed change; c is the wave speed; and p is the density of the fluid medium, for example, blood. The severity of coronary stenosis can be determined according to an equation that is similar to conventional FFR. In conventional FFR, the measurement of stenosis (that is, the FFR ratio defined above) is determined by: Conventional FFR = (distal pressure) / (proximal pressure) (Equation 3)
    [025] The FFR measurement can alternatively be expressed in terms of the back pressure flow reserve, that is, without the back pressure effects that originate from the microcirculatory end: advance pressure flow reserve = (distal P +) / ( proximal P-) (Equation 4)
    [026] Figure 1 shows a schematic diagram of a vessel 10 for transporting a fluid medium 11 in an axial direction 12 in the direction of the vessel. Vessel 10 can be a pipe or tube and in an important context, it can comprise a part of a vessel in the human or animal coronary system. Constriction 15 in vessel 10 exemplifies a target region 16 for which it is desired to measure the effect of that constriction on the flow of fluid through the vessel. In one context, constriction 15 can be a coronary artery stenosis and it is required to determine a measure of the drop in fluid pressure through the constriction to determine a ratio of the maximum flow through the vessel compared to the maximum flow that should occur without the constriction. Regions 5 and 6 represent a first or second location where pressure and velocity measurements can be obtained according to the method to be described below. The first site 5 is on a first side of the target region 15 and the second site 6 is on a second site of the target region 15. The first site 5 can be on the proximal or aortic side of coronary stenosis (or other) and the second site 6 then, it must be on the distal or microcirculatory side of coronary stenosis (or other). It is preferred that the distance from the first site (the proximal or aortic side) of the stenosis is at least 1.5 times the diameter of the vessel in the unrestricted part of the vessel.
    [027] Figure 2 shows an exemplary method 20 for determining a measurement of constriction 15 in vessel 10. A succession of first pressure measurements P1 and a succession of first velocity measurements corresponding to U1 are obtained at the first location 5 (step 21) . A succession of second pressure measurements P2 and a succession of corresponding second speed measurements U2 are obtained at the second location 6 (step 22). Each pressure measurement and its corresponding speed measurement are preferably obtained substantially simultaneously.
    [028] The speed of wave c at each of the first and second locations 5, 6 is determined as a function of the square of the change in pressure dP divided by the square of the corresponding change in speed dU (step 23). The change in pressure dP is preferably determined from the succession pair of the first pressure measurement P1 and, correspondingly, from the succession pair of the second pressure measurements P2. The change in speed dU is preferably determined from the succession pair of the first speed measurement U1 and, correspondingly, from the succession pair of the second speed measurement U2. Most preferably, a succession of pressure measurements and corresponding velocity measurements is taken over a period of time to generate the multiple dP and dU measurements that can be aggregated to improve the signal-to-noise ratio. The wave velocity can be calculated by a succession of pairs of pressure and velocity measurements that are added together and the square root of the sum obtained. The wave speed can therefore be determined by a succession of the measurement times, in each of the first and second locations 5, 6, according to the formula: c = (1 / p) □ (∑dP2 / ∑dU2) ( Equation 5) where p is the specific density of the fluid medium in the vessel. In a preferred context, the fluid medium is blood with a density of 1050 kg / m3.
    [029] An advance pressure change dP + is then determined as a function of the sum of the change in pressure dP and the corresponding (simultaneous) change in speed dU. More preferably, the advance pressure change dP1 + in the first location is determined according to the equation: dP1 + = (pdP1 + pcdU1) / 2 (Equation 6) and the change in advance pressure dP2 + in the second location is determined according to the equation: dP2 + = (pdP2 + pcdU2) / 2 (Equation 7) as shown in steps 24 and 25.
    [030] The values of dP1 + are preferably added or integrated in all successive measurements to obtain an advance pressure value P1 + at the first location (step 26). The dP2 + values are also preferably added or integrated in all successive measurements to obtain an advance pressure value P2 + at the second location (step 27).
    [031] The flow reserve for flow pressures is then determined as a function of the ratio P2 + / P1 + (or, if simple pressure change changes are used, dP2 + / dP1 +). If the first location 5 comprises the proximal or aortic side of the stenosis and the second location 6 comprises the distal or microcirculatory site of the stenosis then the advance pressure flow reserve, Advance FPFR = P + distal / P + proximal. Thus, in a preferred arrangement, the first location 5 is upstream of the target region 15 and the second location 6 is downstream of the target region 15 (assuming the continuous positive flow).
    [032] In the context of the measurement of a coronary stenosis, preferably the successions of the pressure and velocity measurements are made in at least one total cardiac cycle and preferably in a total number of cardiac cycles. The average and maximum values of P1 + and P2 + can be used in the calculation of FPFR to derive a value of average FPFR and FPFRmax. The values of dP1 + and dP2 + used to obtain an advance pressure value P1 + and an advance pressure value P2 + can be taken from the selected parts of one or more cardiac cycles or, as above, in one or more cardiac cycles whole. Preferably, at least five or ten dP1 + and dP2 + measurements are used for each cardiac cycle. Mechanisms
    [033] The appropriate mechanisms for carrying out the methods described above are generally shown in figure 3.
    [034] A pressure sensitive device 30 is used to generate signals indicative of instantaneous pressure at a selected location 5 or 6 in vessel 10. These pressure signals are transmitted in a suitable analog to digital converter 31 to generate a series of measurements pressure as a function of time taken at the selected location, for example the succession of the first pressure measurement P1 and the succession of the second pressure measurements P2. Similarly, a pressure sensitive device 32 is used to generate signals indicative of the instantaneous fluid velocity at the same substantially selected location 5 or 6 as the pressure sensitive device 30. These fluid velocity signals are transmitted in an analog to digital converter. suitable 33 to generate a series of fluid velocity measurements as a function of time taken at the selected location, for example, the succession of the first velocity measurement U1 and the succession of the second velocity measurement U2. The corresponding velocity and pressure measurements are preferably taken at substantially the same time.
    [035] The pressure sensitive device 30 can be either any suitable transducer or other device capable of providing a direct or indirect pressure measurement at a selected location in vessel 10. The pressure sensitive device can be a localized pressure transducer located inside the fluid in vessel 10 at the selected location 5, 6 or it can be a remotely located active or passive sensor using any radiation detectable from the flow stream or its containment vessel that can be used to determine the pressure whether acoustic, electromagnetic, magnetic or otherwise. For example, in the coronary arteries and aorta, PrimeWireTM, FloWireTM and ComboWireTM XT by Volcano Corporation can be used as sensors in situ.
    [036] The fluid velocity sensitive device 32 similarly can be either any suitable transducer or other device capable of providing a direct or indirect measurement of fluid velocity at a selected location in vessel 10. The fluid velocity sensitive device 32 can be an in situ transducer located within the fluid in the vessel at the selected location 5, 6 or can be a remotely located active or passive sensor using any radiation detectable from the flow stream that can be used to determine the speed of the acoustic fluid, electromagnetic, magnetic or otherwise, such as Doppler ultrasound techniques. In the coronary arteries and aorta, the WaveWireTM, FloWireTM and ComboWireTM XT products mentioned above can be used as sensors in situ. The term 'radiation detectable from the fluid flow' is intended to encompass any active or reflected radiation or energy radiation from the fluid alone or any agents or markers loaded into the fluid.
    [037] The same pressure sensitive device 30 can be used to obtain a succession of the first pressure measurement P1 at the first location 5 and the succession of the second pressure measurements P2 at the second location 6, at separate times. Similarly, the same velocity sensitive device 32 can be used to obtain the succession of the first velocity measurement U1 at the first location 5 and the succession of the second velocity measurement U2 at the second location 6, in separate periods. Alternatively, combined sensors, such as the ComboWireTM sensor, can be configured to take measurements of both the first and the second location simultaneously. The ComboWireTM sensor is a steerable guide wire with a pressure transducer mounted near the end and an ultrasound transducer mounted on the end. This can be used to measure the simultaneous pressure and speed of blood flow in blood vessels including both coronary and peripheral vessels.
    [038] Data streams from analog to digital converters 31, 33 are passed in a data recording module 35, preferably implemented by a computer 34. Computer 34 includes a separate pressure flow reserve analysis module 36 for implementing the algorithms described in this one.
    [039] A first processing module 37 (wave speed analysis module) determines a wave speed at the first and second location, preferably according to the equation given by c above (equation 5). A second processing module 38 (pressure analysis module) determines an advance pressure change at the first location, preferably according to the expression by dP1 + given above (equation 6). The second processing module 38 also determines the advance pressure change at the second location, preferably according to the expression by dP2 + given above (equation 7). The c-wave velocity can be determined by the sampling pressure and fluid velocity in one or more entire cardiac cycles at the selected location and the average of these cycles.
    [040] Computer 34 preferably includes an additional computing module 39 for integrating or adding an advance pressure change at the first and second locations according to steps 26 and 27 in Figure 2 and for determining the pressure flow reserve of advance FPFRfor advance preferably according to step 28 of figure 2.
    [041] The advancing FPFR gives a measurement of the severity of coronary stenosis. The measurement produced in this way, that is, using only progressive pressure waves of advancement (originating aortic), is substantially less influenced or not influenced by the regional variation in myocardial contractility or automatic deregulation of the coronary microcirculation. Data processing from computer 34 can be performed in any suitable mechanisms, such as a suitable programmed computer system or in a common construction software / hardware measurement unit of flow velocity pressure measurement. It will be understood that the distribution of computational functions in hardware and software can be handled differently than the exemplary analysis as shown in figure 3 and can be implemented in any suitable combination of hardware and software.
    [042] A debate on the clinical importance of using separate advancing and inverse pressure separation in the assessment of coronary stenosis is provided in Annex 1.
    [043] While the techniques of this invention have been mainly described in connection with analysis of stenosis or other constrictions in the coronary system, the techniques described may also be applicable to other systems such as the renal circulatory system or any other system where the flow of the paste fluid in a constriction is governed by progressive forward and reverse pressure waves.
    [044] Other forms of realization are intentionally within the scope of the attached claims. APPENDIX 1
    [045] This new advance pressure flow reserve technique has several key therapeutic advantages in conventional FFR. 1. estimate of coronary stenosis immediately after acute myocardial infarction 2. estimate of coronary stenosis within 5 days of acute coronary syndrome 3. estimate of coronary stenosis in patients with abnormalities of movement of the regional wall 4. estimate of coronary stenosis in patients with disease microcirculatory 5. abandoned need for adenosine administration.
    [046] The benefits can significantly increase the number of patients suitable for the FFR-type estimate and have a positive impact on the total numbers of coronary revascularization cases performed. Currently in the UK, approximately 30% of the case load is for acute admissions in patients with acute myocardial infarction or acute coronary syndrome. In this population, FFR is contraindicated and has been found to be inconsistent at best and often unsafe.
    [047] The advance pressure flow reserve overcomes or alleviates these limitations for the separation of proximal or distal components from the pressure waveform. Since the advance pressure flow reserve is able to remove reverse pressure from the advance pressure component, it negates the need to administer considerable vasodilators such as adenosine.
    [048] These have several specific advantages. 1. Overcomes the limitations of adenosine intolerance (asthma, COPD etc.) 2. Overcomes the limitations of adenosine resistance 3. Avoids the insertion of the secondary central venous sheath 4. Reduces the total case time.
    [049] From the pilot data, the inventors have observed the wide differences in the ratio between waves of proximal and distal origin in the normal and severely hypokinetic ventricles. In some cases, greater than 80% reduction is observed in the proximal / distal ratio in the artery that extends below the severely hypokinetic territory when compared to an artery that extends below the normally contracting myocardium. This is shown in figure 4. The pressure and flow velocity were recorded using the intra-arterial wires in the left anterior descending artery and the calculated wave intensity for each artery. In the ventricle with preserved function, the proximal / distal ratio was approximately 1, considering that in the artery extending below a segment of severely hypokinetic function this ratio is markedly increased. This suggests regional myocardial function differently affects the pressure originating from the proximal and distal origins.
    [050] The fractional flow reserve (FFR) assumes that the coronary pressure originates only from the proximal (aortic) end of the artery and that the forces exerted on the intramural coronary vessels by the pressure of the transmitted cavity and contracting the myocardium do not contribute to coronary artery pressure. The inventors have shown that this is not the case, but instead of coronary pressure it is made up of approximately 50% of progressive progression (aortic origin) and 50% of progressive reverse pressure components (see figure 4, left graph). It is believed that in patients with regional variation in myocardial contractility: (i) progressive reverse pressure is markedly reduced (as shown in the right graph in figure 4) and (ii) that it is not possible to determine without a failure in FFR is due to a stricture hemodynamically significant coronary artery disease or regional variation in myocardial contractility. Using the separate pressure components as described in this patent application allows the hemodynamic importance of coronary stenosis to be quantified regardless of regional variation in myocardial contractility. This technique can be adopted routinely in clinical practice and negates the need for routine administration of intravenous adenosine.
    [051] Fractional flow reserve (FFR) is increasingly used to estimate the physiological importance of coronary stenosis1,2,3,4 and stent placement sufficiency5 in the cardiac catheter laboratory. This technique is based on a simple premise that is greater in stenosis and greater in diverging pressure between the aorta and downstream of the stenosis.
    [052] FFR is based on the assumption that pressure changes elevate purely from the aortic end of the coronary artery. However, several studies including your own have clearly shown that coronary artery pressure is influenced by changes in pressure from both ends of the vessels6-9. Probably the most widely accepted models of coronary artery flow are in the intra-myocardial pump6 and elastic models of time variation9. Both predict the existence of retrograde coronary blood flow during systole as a result of elevated intramiocardial pressure and myocardial contraction causing compression of the smaller microcirculatory vessels6. Such retrograde flow was confirmed by measurements in dogs in vivo using needle probe video10 and doppler flow probe11. This indicates the presence of a considerable reverse direct pressure gradient in systole. His work8 has characterized this inverse pressure gradient as an inverse progressive wave in the coronary arteries of humans in advancing systole due to the compression of the coronary microvasculature. In diastole, there is a corresponding 'suction' of blood in the coronary microvasculature as a result of decompression of intramural vessels accompanying myocardial relaxation. We have recently demonstrated that this inverse suction wave is reduced in left ventricular hypertrophy8. Therefore, it may be a component of progressive reverse pressure less in other circumstances that impair the lusitropic behavior of the myocardial region provided by the particular coronary artery. The existence of pressure gradients generated by the contraction and relaxation of the myocardium will significantly affect the measurement of FFR, perhaps by 50% or more (Figure 5).
    [053] The limitations of the hypothesis of a unidirectional pressure gradient implicit in the calculation of FFR (ie there is no significant progressive reverse contribution to coronary pressure) are recognized as a potential source of error in microvascular disease and left ventricular dysfunction2,12, 13. However, until recently, there is no significance of procedure with this, that is, the absence of a technique to separate the coronary pressure waveform in its progressive components of advances and inverses in human patients.
    [054] Recently we have developed a new technique (the single point technique) that, in combination with wave intensity analysis, enables the coronary pressure to be separated into its forward and reverse components on the basis of simultaneous records and flow rate14 ( Figure 6). Such measurements are now completely possible using a commercially available combined pressure flow wire designed for intracoronary use (Combiwire, Volcano) and negates the need for adenosine administration. Using this technique in in-vivo human studies, we have identified the waves responsible for coronary blood flow and separated from the coronary pressure waveform in its progressive (progressive aortic) and inverse (originating microcirculatory) components.
    [055] These studies demonstrate the component of progressive reverse pressure in human coronary arteries is of the same magnitude as the component of progressive pressure of wide advancement. Since coronary pressure is just as a result of the reverse progressive pressure components14 as it is of the progressive advance components, if they are interested in the advance pressure spread it is more appropriate to measure FFR using the isolated forward progressive pressure component. By thus removing the component of progressive reverse pressure, they can eliminate the influence of regional variation of left ventricular function, microvascular dysfunction and right atrial pressure allowing a more accurate estimate of the hemodynamic importance of a stenosis.
    [056] Figure 6 shows a series of graphs illustrating the separation of the total measured pressure in its forward and reverse components as a function time. Simultaneous pressure and flow velocity were measured in the cinchfunctional artery of a 47-year-old man. The wave intensity analysis was applied to separate the coronary pressure in its components of advances of inverse progressive advances. Advance pressure appears different from aortic pressure due to the wide impedance error between the coronary artery and the aorta. In such locations the reverse progressive wave is reflected back into the coronary as an expansion (or suction) wave that reduces pressure. Reference List (1) Dawkins KD, Gershlick T, from BM ET AL. Percutaneous coronary intervention: recommendations for good practice and training. Heart December 2005; 91 Suppl 6: vi1-27. (2) Blows LJ, Redwood SR. The pressure wire in practice. Heart April 2007; 93 (4): 419-22. (3) Pijls NH, van Son JA, Kirkeeide RL, de BB, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation April 1993; 87 (4): 1354-67. (4) Pijls NH, de BB, Peels K et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med June 1996 27; 334 (26): 1703-8. (5) Pijls NH, Klauss V, Siebert U ET AL. Coronary pressure measurement after stenting predicts adverse events at follow-up: a multicenter registry. Circulation June 2002 25; 105 (25): 2950-4. (6) Spaan JA, Breuls NP, Laird JD. Diastolic-systolic coronary flow differences are caused by intramyocardial pump action in the anesthetized dog. Circ Res September 1981; 49 (3): 584-93. (7) Gregg DE, Sabiston DC. Effect of cardiac contraction on coronary blood flow. Circulation January 1957; 15 (1): 14-20. (8) Davies JE, Whinnett ZI, Francis DP et al. Evidence of a dominant backward-propagating “suction” wave responsible for diastolic coronary filling in humans, attenuated in left ventricular hypertrophy. Circulation April 2006 11; 113 (14): 1768-78. (9) Krams R, Sipkema P, Westerhof N. Varying elastance concept may explain coronary systolic flow impediment. Am J Physiol November 1989; 257 (5 Pt 2): H1471-H1479. (10) Hiramatsu O, Goto M, Yada T et al. In vivo observations of the intramural arterioles and venules in beating canine hearts. J Physiol June 1998 1; 509 (Pt 2): 619-28. (11) Chilian WM, Marcus ML. Phasic coronary blood flow velocity in intramural and epicardial coronary arteries. Circ Res June 1982; 50 (6): 775-81. (12) Siebes M, Chamuleau SA, Meuwissen M, Piek JJ, Spaan JA. Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model. Am J Physiol Heart Circ Physiol October 2002; 283 (4): H1462-H1470. (13) Coronary flow is not that simple! Spaan JA. Heart. May 2009; 95 (9): 761-2 (14) Davies JE, Hadjiloizou N, Francis DP, Hughes AD, Parker KH, Mayet J. The role of the coronary microcirculation in determining blood flow. Artery Research 1 [S1], S31-S32. 2006. Ref Type: Abstract (15) Kim RJ, Wu E, Rafael A et al. The use of contrast- enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med November 2000 16; 343 (20): 1445-53. (16) Perera D, Biggart S, Postema P et al. Right atrial pressure: can it be ignored when calculating fractional flow reserve and collateral flow index J Am Coll Cardiol November 2004 16; 44 (10): 2089-91. (17) Davies JE, Whinnett ZI, Francis DP et al. Use of simultaneous pressure and speed measurements to estimate arterial wave speed at a single site in humans. Am J Physiol Heart Circ Physiol February 2006; 290 (2): H878-H885. (18) Parker KH, Jones CJ, Dawson JR, Gibson DG. What stops the flow of blood from the heart Heart Vessels 1988; 4 (4): 241-5. (19) Davies JE, Parker KH, Francis DP, Hughes AD, Mayet J. What is the role of the aorta in directing coronary blood flow Heart December 2008; 94 (12): 1545-7. (20) Hadjiloizou N, Davies JE, Malik IS et al. Differences in cardiac microcirculatory wave patterns between the proximal left mainstem and Proximal right coronary artery. Am J Physiol Heart Circ Physiol September 2008; 295 (3): H1198-H1205.
    权利要求:
    Claims (14)
    [0001]
    1. Method (20) to determine a measure of constriction (15) in a vessel (10) that carries a fluid medium (11), characterized by the fact that the method comprises the steps of: a) taking (21) a succession the first pressure measurements P1 and a succession of first velocity measurements corresponding to U1 at a first location (5) within the vessel (10), the first location (5) being within a first side of a target region (16); b) take (22) a succession of second pressure measurements P2 and a succession of corresponding second speed measurements U2 at a second location (6) inside the vessel (10), the second location (6) being on a second side of the target region (16); c) for each location, determine (23) the speed of wave c in the fluid medium (11) as a function of the square of a change in pressure dP divided by the square of the corresponding change in speed dU; d) for the first location (5), determine (24) an advance pressure change dP1 + as a function of the sum of the change in pressure dP1 and the change in speed dU1; e) for the second location (6), determine (25) an advance pressure change dP2 + as a function of the sum of the change in pressure dP2 and the change in speed dU2; f) determining (28) a separate advance flow reserve indicative of the pressure drop across the target region (16) as a function of the ratio of dP2 + / dP1 +.
    [0002]
    2. Method according to claim 1, characterized by the fact that the first side of the target region (16) is upstream of the target region and the second side is downstream of the target region.
    [0003]
    3. Method according to claim 1, characterized by the fact that step c) comprises determining (23) the speed of wave c at each location according to the equation c = (1 / p) ^ (∑dP2 / ∑ dU2), where p is the specific density of the fluid medium (11) in the vessel (10).
    [0004]
    4. Method according to claim 1, characterized by the fact that steps d) and e) comprise determining (24, 25) said pressure changes of advances dP1 + and dP2 + according to the equations: dP1 + = (dP1 + pcdU1 ) / 2 and dP2 + = (dP2 + pcdU2) / 2.
    [0005]
    5. Method according to claim 1, characterized by the fact that step f) includes integrating (26, 27) or adding multiple values of dP1 + and dP2 + to obtain pressure values of feeds P1 + and P2 + and determining (28) the separate advance flow reserve as a function of the P2 + / P1 + ratio.
    [0006]
    6. Method according to claim 1, characterized by the fact that it is applied to a vessel (10) in which there is a source of buoyancy pressure on each side of the target region (16).
    [0007]
    Method according to claim 6, characterized in that it is applied to a vessel (10) in the human or animal cardiac circulatory system.
    [0008]
    Method according to claim 7, characterized in that the succession of measurements of the first and second pressure and the succession of first and second velocity measurements are obtained (21, 22) in at least one complete cardiac cycle.
    [0009]
    9. Method according to claim 1, characterized by the fact that the corresponding pressure and velocity measurements are obtained simultaneously.
    [0010]
    10. Apparatus for determining a measure of constriction (15) in a vessel (10) that carries a fluid medium (11), characterized by the fact that the apparatus comprises: a pressure sensor (30) and a speed sensor (32 ) to obtain (21, 22) a succession of pressure and velocity measurements in the vessel (10) in at least one first location (5) upstream of a target region (16) and a second location (6) downstream of the region target (16); a processing module (35, 36) adapted to: receive a succession of the first pressure measurements P1 and a succession of corresponding first speed measurements U1 obtained at the first location (5) within the vessel (10); receiving a succession of second pressure measurements P2 and a succession of corresponding second speed measurements U2 obtained at the second location (6) within the vessel (10); for each location, determine the speed of wave c (23) in the fluid medium (11) as a function of the square of a change in pressure dP divided by the square of the corresponding change in speed dU; for the first location (5), determine (24) an advance pressure change dP1 + as a function of the sum of the change in pressure dP1 and the change in speed dU1; and for the second location (6), determine (25) an advance pressure change dP2 + as a function of the sum of the change in pressure dP2 and the change in speed dU2; and determining (28) a separate advance flow reserve indicative of the pressure drop across the target region (16) as a function of the ratio of dP2 + / dP1 +.
    [0011]
    11. Apparatus according to claim 10, characterized by the fact that the processing module (36) is still adapted to determine (23) the speed of wave c at each location according to equation c = (1 / p) ^ (∑dP2 / ∑dU2), where p is the specific density of the fluid medium (11) in the vessel (10).
    [0012]
    12. Apparatus according to claim 10, characterized by the fact that the processing module (36) is still adapted to determine (24, 25) said advancing pressure changes dP1 + and dP2 + according to the equations: dPi + = (dPi + pcdUi) / 2 and dP2 + = (dP2 + pcdUi) / 2.
    [0013]
    13. Apparatus according to claim 10, characterized by the fact that the processing module (36) is still adapted to integrate (26, 27) or add the multiple values of dP1 + and dP2 + to obtain advance pressure values P1 + and P2 + and determine (28) the separate advance flow reserve as a function of the P2 + / P1 + ratio.
    [0014]
    Apparatus according to claim 10, characterized by the fact that it also includes means for monitoring a heart rate and for controlling said pressure sensor and said speed sensor to collect said succession of pressure measurements and said succession of speed measurements during a complete cardiac cycle.
    类似技术:
    公开号 | 公开日 | 专利标题
    BR112012022685B1|2021-02-09|method and apparatus for determining a measure of constriction in a vessel carrying a fluid medium
    JP3234462B2|2001-12-04|Cardiovascular function evaluation device
    JP6700279B2|2020-05-27|System and method for assessing cardiac system by determining minimum distal pressure/arterial pressure | ratio
    Hall et al.1998|Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure
    Hasanin2015|Fluid responsiveness in acute circulatory failure
    Bednarik et al.1995|Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep
    US8632470B2|2014-01-21|Assessment of pulmonary vascular resistance via pulmonary artery pressure
    Monnet et al.2018|Assessment of fluid responsiveness: recent advances
    Little et al.1985|Effect of regional ischemia on the left ventricular end-systolic pressure-volume relation in chronically instrumented dogs
    Augusto et al.2012|Interpretation of blood pressure signal: physiological bases, clinical relevance, and objectives during shock states
    JP2019521730A|2019-08-08|Device and method for stratifying patients for renal denervation based on measurements of intravascular pressure and wall thickness
    Pinsky2006|Pulmonary artery occlusion pressure
    Florenzano et al.1987|Left ventricular mechanical adaptation to chronic aortic regurgitation in intact dogs
    Lee et al.1987|Application of end-systolic pressure-volume and pressure-wall thickness relations in conscious dogs
    Adiputra et al.2015|Clinical relevance of coronary fractional flow reserve: art-of-state
    Dell'Italia1990|Mechanism of postextrasystolic potentiation in the right ventricle
    Ilebekk et al.1978|Cardiac performance: independence of adrenergic inotropic and chronotropic effects
    Jakljević et al.2012|Detection of myocardial ischemia in diabetic patients: the limitations of myocardial perfusion imaging
    Ko2008|Christina Kolyva
    Rapaccini et al.1996|Doppler ultrasound evaluation of acute effects of cigarette smoking on portal blood flow in man
    JP2021534856A|2021-12-16|Kidney denervation preparation
    Casadonte et al.2020|Usefulness of Proximal Coronary Wave Speed for Wave Intensity Analysis in Diseased Coronary Vessels
    Passerini et al.2017|Patient-Specific Modeling of the Coronary Circulation
    Leone et al.2017|Understanding Fractional Flow Reserve
    Gaasch2016|Right Heart Pressure Transients and Pulmonary Venous Pressure
    同族专利:
    公开号 | 公开日
    BR112012022685A2|2018-05-22|
    WO2011110817A2|2011-09-15|
    RU2556782C2|2015-07-20|
    JP5663041B2|2015-02-04|
    RU2012143201A|2014-04-20|
    GB2479340A|2011-10-12|
    JP2013521092A|2013-06-10|
    EP2544585B1|2014-01-08|
    ES2457268T3|2014-04-25|
    GB201003964D0|2010-04-21|
    CN102905614A|2013-01-30|
    WO2011110817A3|2011-11-03|
    EP2544585A2|2013-01-16|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    SU1467429A1|1985-11-25|1989-03-23|Пермское производственное объединение "Моторостроитель" им.Я.М.Свердлова|Method of estimating injury of vasa by atherosclerosis|
    US6471656B1|1999-06-25|2002-10-29|Florence Medical Ltd|Method and system for pressure based measurements of CFR and additional clinical hemodynamic parameters|
    AU7443200A|1999-09-22|2001-04-24|Florence Medical Ltd.|A method and system for determination of ffr based on flow rate measurements|
    US6585660B2|2001-05-18|2003-07-01|Jomed Inc.|Signal conditioning device for interfacing intravascular sensors having varying operational characteristics to a physiology monitor|
    JP3683256B2|2003-02-28|2005-08-17|コーリンメディカルテクノロジー株式会社|Arterial stenosis diagnostic device|
    US8277386B2|2004-09-27|2012-10-02|Volcano Corporation|Combination sensor guidewire and methods of use|
    CN101277644A|2005-08-25|2008-10-01|密理克公司|Vascular resistance gauge|
    KR20170081278A|2008-09-11|2017-07-11|어시스트 메디칼 시스템즈, 인크.|Physiological sensor delivery device and method|
    NZ592387A|2008-09-22|2014-01-31|Dtherapeutics Llc|Devices, systems, and methods for determining fractional flow reserve|EP2656051B1|2011-05-31|2021-11-03|Lightlab Imaging, Inc.|Multimodal imaging system|
    WO2013019840A1|2011-08-03|2013-02-07|Lightlab Imaging, Inc.|Systems, methods and apparatus for determining a fractional flow reserve|
    WO2013072685A2|2011-11-14|2013-05-23|Paradigm Flow Services Limited|Method of assessing and condition monitoring of fluid conduits and apparatus therefor|
    EP2804525A4|2012-01-19|2015-12-09|Volcano Corp|Interface devices, systems, and methods for use with intravascular pressure monitoring devices|
    US20140086461A1|2012-09-25|2014-03-27|The Johns Hopkins University|Method and system for determining time-based index for blood circulation from angiographic imaging data|
    EP2934308B1|2012-12-21|2022-02-09|Philips Image Guided Therapy Corporation|Wireless interface devices, and systems for use with intravascular pressure monitoring devices|
    JP6532857B2|2013-03-15|2019-06-19|ボルケーノ コーポレイション|Interface device, system and method for use with an intravascular pressure monitoring device|
    US10835183B2|2013-07-01|2020-11-17|Zurich Medical Corporation|Apparatus and method for intravascular measurements|
    US10702170B2|2013-07-01|2020-07-07|Zurich Medical Corporation|Apparatus and method for intravascular measurements|
    KR20210111325A|2013-07-30|2021-09-10|하트플로우, 인크.|Method and system for modeling blood flow with boundary conditions for optimized diagnostic performance|
    CN106456026B|2014-04-04|2020-09-18|圣犹达医疗系统公司|Intravascular pressure and flow data diagnostic systems, devices, and methods|
    JP6596078B2|2014-09-11|2019-10-23|コーニンクレッカフィリップスエヌヴェ|Bedside controller and related devices, systems and methods for assessing blood vessels|
    CN105326486B|2015-12-08|2017-08-25|博动医学影像科技（上海）有限公司|Vascular pressure difference and the computational methods and system of blood flow reserve fraction|
    US11154205B2|2016-03-15|2021-10-26|King's College London|Method and system for pressure drop estimation|
    GB201604873D0|2016-03-22|2016-05-04|Imp Innovations Ltd|Fluid flow analysis|
    EP3831307A1|2019-12-02|2021-06-09|Koninklijke Philips N.V.|An apparatus for determining a physiological parameter relating to a vessel|
    法律状态:
    2018-05-29| B08F| Application fees: dismissal - article 86 of industrial property law|Free format text: REFERENTE A 7A ANUIDADE. |
    2018-09-18| B08G| Application fees: restoration|
    2020-07-07| B06U| Preliminary requirement: requests with searches performed by other patent offices: suspension of the patent application procedure|
    2020-12-01| B09A| Decision: intention to grant|
    2021-02-09| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 10/03/2011, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    GB1003964A|GB2479340A|2010-03-10|2010-03-10|Method and apparatus for the measurement of a fluid flow restriction in a vessel|
    GB1003964.2|2010-03-10|
    PCT/GB2011/000344|WO2011110817A2|2010-03-10|2011-03-10|Method and apparatus for the measurement of a fluid flow restriction in a vessel|
    [返回顶部]