SYSTEM AND METHOD FOR DETERMINING THE MICROVASCULAR RESISTANCE RESERVE

Abstract

The invention relates to a method for determining the microvascular resistance reserve, MRR, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, which method comprises the step of during rest condition of the patient: measuring the blood flow, Q.sub.rest, through the coronary artery; and further comprising the step of during rest condition or during maximum hyperemia of the patient: measuring the blood pressure, P.sub.a, at a position proximal in the coronary artery or proximally of any stenosis, if present; and further comprising the steps of during maximum hyperemia of the patient: measuring the blood flow, Q.sub.max, through the coronary artery; and measuring the blood pressure, P.sub.d, at a position distal in the coronary artery or distally of any stenosis, if present, and wherein the microvascular resistance reserve, MRR, is determined by the additional step of calculating the microvascular resistance reserve as

[00001]$MRR=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,hyper}}.$

Claims

1. A method for determining microvascular resistance reserve, MRR, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, which method comprises the step of during rest condition of the patient: measuring blood flow, Q.sub.rest, through the coronary artery; and further comprising the step of during rest condition or during maximum hyperemia of the patient: measuring blood pressure, P.sub.a, at a position proximal in the coronary artery or proximally of any stenosis if present; and further comprising the steps of during maximum hyperemia of the patient: measuring blood flow, Q.sub.max, through the coronary artery; and measuring blood pressure, P.sub.d,hyper, at a position distal in the coronary artery or distally of any stenosis if present, wherein the microvascular resistance reserve is determined by the additional step of calculating the microvascular resistance reserve as $\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,\mathrm{hyper}}}.$

2. The method according to claim 1, wherein the step of measuring the blood pressure, P.sub.a, at a position proximal in the coronary artery or proximally of any stenosis, if present, comprises the step of measuring the aortic blood pressure.

3. The method according to claim 1, wherein the step of measuring the blood pressure at a position proximal in the coronary artery or proximally of any stenosis, if present, is performed during rest condition of the patient.

4. The method according to claim 3, further comprising calculating microvascular resistance, R.sub.micro,rest, at rest condition of the patient as R.sub.micro,rest=P.sub.a, rest/Q.sub.rest.

5. A method for determining microvascular resistance reserve, MRR, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, which method comprises: determining a value of Coronary Flow Reserve, CFR, of the coronary artery of the patient; determining a value of Fractional Flow Reserve, FFR, of the coronary artery of the patient; determining a value of blood pressure during rest condition of the patient, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present; and determining a value of blood pressure during maximum hyperemia of the patient, P.sub.a, hyper, at a position proximal in the coronary artery or proximally of any stenosis if present, wherein the microvascular resistance reserve, MRR, is determined by the additional step of calculating the microvascular resistance reserve as $\mathrm{MRR}=\frac{\mathrm{CFR}}{\mathrm{FFR}}\frac{P_{a.\mathrm{rest}}}{P_{d,\mathrm{hyper}}}.$

6. The method according to claim 5, wherein determining the value of CFR comprises: measuring, during rest condition of the patient, blood flow, Q.sub.rest, through the coronary artery; and measuring, during maximum hyperemia of the patient, blood flow, Q.sub.max, through the coronary artery, wherein CFR is determined by calculating CFR=Q.sub.max/Q.sub.rest.

7. The method according to claim 6, wherein said determining the value of CFR comprises conducting at least one measurement using a non-invasive technique such as Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography, or echocardiography.

8. The method according to claim 5, wherein said determining the value of blood pressure during rest condition of the patient, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present comprises measuring blood pressure substantially simultaneously with the step of determining the value of CFR.

9. The method according to claim 5, wherein determining the value of FFR comprises, during maximum hypermia of the patient: measuring blood pressure, P.sub.a, hyper, at a position proximal in the coronary artery or proximally of any stenosis if present; and measuring blood pressure, P.sub.d, hyper, at a position distal in the coronary artery or distally of any stenosis if present, wherein FFR is calculated as FFR=P.sub.d, hyper/P.sub.a, hyper.

10. The method according to claim 9, wherein determining the value of FFR comprises conducting at least one measurement using an invasive technique such as a pressure or guiding catheter or a sensor-tipped guide wire.

11. The method according to claim 9, wherein said-determining the value of FFR comprises conducting at least one measurement using a non-invasive technique such as Computed Tomography.

12. The method according to claim 5, wherein measurements conducted to determine the value of CFR and to determine the value of FFR are performed at different times.

13. The method according to claim 5, wherein at least one of determining the value of CFR, determining the value of FFR, determining the value of P.sub.a,rest and determining the value of P.sub.a,hyper comprises obtaining a previously calculated or measured value.

14. A method for determining microvascular resistance at rest condition, R.sub.micro,rest, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, which method comprises, during rest condition of the patient: measuring blood flow, Q.sub.rest, through the coronary artery; and measuring blood pressure, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present, wherein the microvascular resistance at rest condition is calculated as R.sub.micro,rest=P.sub.a, rest/Q.sub.rest.

15. The method according to claim 14, wherein said measuring Q.sub.rest is conducted using a non-invasive technique such as Computed Tomography, Magnetic Resonance Imaging or Positron Emission Tomography, and wherein said measuring P.sub.a, rest is conducted using a non-invasive technique such as using a sphygmomanometer.

16. A processing unit comprising means for carrying out the method according to claim 1.

17. A computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method of claim 5.

18. A system for determining microvascular resistance reserve, MRR, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, comprising: a processing unit; a first flow measuring system configured for measuring the blood flow, Q.sub.rest, through the coronary artery during rest condition of the patient; a first pressure measuring instrument configured for measuring the blood pressure, P.sub.a, at a position proximal in the coronary artery or proximally of any stenosis, if present, during rest condition or during maximum hyperemia of the patient; a second flow measuring system configured for measuring the blood flow, Q.sub.max, through the coronary artery during maximum hyperemia of the patient; and a second pressure measuring instrument configured for measuring the blood pressure, P.sub.d,hyper, at a position distal in the coronary artery or distally of any stenosis, if present, during maximum hyperemia of the patient, wherein the processing unit is configured for obtaining blood flow measurements Q.sub.rest, Q.sub.max from the first and second flow measuring systems and obtaining blood pressure measurements P.sub.a, P.sub.d, hyper from the first and second pressure measuring instruments, and wherein the processing unit is further configured for calculating the microvascular resistance reserve as $\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,\mathrm{hyper}}}.$

19. The system according to claim 18, wherein the first flow measuring system and the second flow measuring system are the same flow measuring system.

20. The system according to claim 18, wherein the system further comprises: a display unit configured for receiving the calculated value of the microvascular resistance reserve from the processing unit and displaying said calculated value.

21. The system according to claim 18, wherein the first pressure measuring instrument comprises a pressure catheter or a guiding catheter.

22. The system according to claim 18, wherein the first pressure measuring instrument and/or the second pressure measuring instrument comprises a sensor-tipped guide wire.

23. The system according to claim 18, wherein the first flow measuring system and/or the second flow measuring system is a system which utilizes a invasive or non-invasive flow or flow substitute measurement.

24. A system for determining microvascular resistance reserve, MRR, in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, comprising a processing unit and an interface, wherein said processing unit is configured to, in response to at least one signal received via said interface comprising data indicative of the Coronary Flow Reserve, CFR, and the Fractional Flow Reserve, FFR, of the coronary artery of the patient, and further indicative of the blood pressure, P.sub.a, rest, during rest condition of the patient at a position proximal in the coronary artery or proximally of any stenosis if present, and of the blood pressure, P.sub.a, hyper, during maximum hyperemia of the patient at a position proximal in the coronary artery or proximally of any stenosis if present, determine the microvascular resistance reserve as $\mathrm{MRR}=\frac{\mathrm{CFR}}{\mathrm{FFR}}\frac{P_{a.\mathrm{rest}}}{P_{d,\mathrm{hyper}}}.$

25. A system for determining microvascular resistance, R.sub.micro,rest, at rest condition in the myocardium perfused by a normal or a stenotic coronary artery of a human patient, comprising a processing unit and an interface, wherein said processing unit is configured to, in response to at least one signal received via said interface comprising data indicative of the blood flow, Q.sub.rest, through the coronary artery during rest condition of the patient and of the blood pressure, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present during rest condition of the patient, determine the microvascular resistance at rest condition as R.sub.micro,rest=P.sub.a, rest/Q.sub.rest.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Above discussed and other aspects of the present invention will now be described in more detail using the appended drawings, wherein:

[0062] FIG. 1 illustrates schematically the coronary circulation,

[0063] FIG. 2 shows a flow chart of an embodiment of the method according to the first aspect of the invention,

[0064] FIG. 3 shows a flow chart of an embodiment of the method according to the third aspect of the invention,

[0065] FIG. 4 shows a flow chart of an embodiment of the method according to the third aspect of the invention,

[0066] FIG. 5 illustrates schematically a system according to the second aspect of the invention,

[0067] FIG. 6 illustrates schematically a system according to the fifth aspect of the invention, and

[0068] FIG. 7 illustrates schematically a system according to the sixth aspect of the invention.

DETAILED DESCRIPTION

[0069] In FIG. 1, the letter A indicates the aorta, the letter B indicates the epicardial artery, and the letter C indicates the microcirculation; and, further, P.sub.a is the pressure proximally of a stenosis and P.sub.d is the pressure distally of the stenosis, and R.sub.epi is the resistance of the stenosis. In a normal, non-stenotic vessel R.sub.epi=0, and P.sub.a=P.sub.d. Then, during rest condition of the patient, the microvascular resistance can be written as:

R.sub.micro,rest,N=P.sub.a,rest/Q.sub.rest,N

[0070] (where the suffix “N” indicates a completely normal coronary artery)

[0071] or simply

R.sub.micro,rest=P.sub.a,rest/Q.sub.rest

[0072] In the presence of an epicardial disease, R.sub.epi>0, and the epicardial disease can be focal but also diffuse. The microvascular resistance in this stenotic case can, during rest condition of the patient, be written as:

R.sub.micro,rest,sten=P.sub.d,rest/Q.sub.rest,sten

[0073] (where the suffix “sten” indicates the presence of a stenosis).

[0074] One may note that R.sub.micro,rest,sten<R.sub.micro,rest,N because the presence of R.sub.epi induces an equivalent compensatory decrease of R.sub.micro,rest,N in order to keep resting blood flow (Q.sub.rest) constant (autoregulatory response of the coronary circulation). Therefore R.sub.micro,rest,sten can also be written as:

[00011]$R_{\mathrm{micro},\mathrm{rest},\mathrm{sten}}=R_{\mathrm{micor},\mathrm{rest},N}-R_{\mathrm{epi}}\mathrm{or}$$\begin{array}{c}{R}_{\mathrm{micro},\mathrm{rest},N}=R_{\mathrm{micro},\mathrm{rest},\mathrm{sten}}+R_{\mathrm{epi}}\\ =\frac{P_{d,\mathrm{rest}}}{Q_{\mathrm{rest},\mathrm{sten}}}+\frac{P_{a,\mathrm{rest}}-P_{d,\mathrm{rest}}}{Q_{\mathrm{rest},\mathrm{sten}}}\\ =P_{a,\mathrm{rest}}/Q_{\mathrm{rest},\mathrm{sten}}\end{array}$

[0075] However, since Q.sub.rest,sten=Q.sub.rest,N, this can be rewritten as:

R.sub.micro,rest=P.sub.a,rest/Q.sub.rest  (1)

[0076] The pressure P.sub.a, rest, which is the pressure measured proximally of the stenosis, can preferably be measured as the aortic pressure and can be measured at the entrance of the coronary artery, and can then be measured with a so-called guiding or pressure catheter, and Q.sub.rest is the measured resting blood flow, which can be measured with a thermodilution technique; or the blood flow can be measured or estimated with any other suitable invasive or non-invasive technique as will be discussed below. It can further be noted that Equation (1) for calculating the microvascular resistance at rest is universally valid and is not dependent on presence or absence of an epicardial disease.

[0077] The equations above were derived for rest condition. During hyperemic conditions of the patient, i.e. when the microvascular resistance is at a minimum and the blood flow is at a maximum, we have for a normal, non-stenotic vessel P.sub.a, hyper=P.sub.d, hyper, and:

R.sub.micro,min,N=P.sub.a,hyper/Q.sub.max,N

Or simply

R.sub.micro,min=P.sub.a,hyper/Q.sub.max

[0078] In the presence of an epicardial disease, which can be focal or diffuse, there is an additional resistance R.sub.epi, and during hyperemia, when the microvascular resistance is at a minimum and the blood flow is at a maximum, then:

R.sub.micro,min,sten=P.sub.d,hyper/Q.sub.max,sten  (2b)

[0079] and because R.sub.micro,min,sten=R.sub.micro,min,N, Equation (2b) can be written as:

R.sub.micro,min=P.sub.d,hyper/Q.sub.max  (2)

[0080] where P.sub.d, hyper is the distal coronary pressure as measured distally of a stenosis during hyperemic conditions of the patient, and where the blood flow Q.sub.max is simultaneously measured by thermodilution or by any other suitable invasive or non-invasive method for measuring blood flow during hyperemia.

[0081] Microvascular resistance reserve (MRR) is a novel quantity within the field of coronary medicine; and despite its apparent usefulness it has never before been measured and calculated in absolute terms. The microvascular resistance reserve (MRR) is defined as:

[00012]$\mathrm{MRR}=\frac{R_{\mathrm{micro},\mathrm{rest}}}{R_{\mathrm{micro},\min }}$

[0082] (with R.sub.micro,rest as not confounded by epicardial disease) which by substituting R.sub.micro,rest with Equation (1) and R.sub.micro,min with Equation (2) can be written as:

[00013]$\begin{array}{cc}\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_{a.\mathrm{rest}}}{P_{d,\mathrm{hyper}}}& \left(3\right)\end{array}$

[0083] with P.sub.a, rest measured at rest and P.sub.d, hyper measured at hyperemia

[0084] It can be noted that MRR as defined above is a universally valid value of microvascular resistance reserve (MRR) and is independent of the presence or absence of an epicardial disease.

[0085] This latter property is a unique feature of this novel index.

[0086] FIG. 2 shows a flow chart of an embodiment of the method according to the first aspect of the invention. The method comprises measuring 1 blood flow, Q.sub.rest, through the coronary artery; and further comprising the step of during rest condition or during maximum hyperemia of the patient measuring 2 blood pressure, P.sub.a, at a position proximal in the coronary artery or proximally of any stenosis if present. The method further comprises the steps of during maximum hyperemia of the patient measuring 3 blood flow, Q.sub.max, through the coronary artery; and measuring 4 blood pressure, P.sub.d,hyper, at a position distal in the coronary artery or distally of any stenosis if present. The microvascular resistance reserve is determined by the additional step of calculating 5 the microvascular resistance reserve as

[00014]$\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,\mathrm{hyper}}}$

[0087] The pressure measurements required by the present method are all well known to the skilled person and are in particular practiced during measurement of the fractional flow reserve (FFR), which is a standard technique in medical examinations of the coronary artery. During FFR measurements the presence and the position of a stenosis, if any, are determined. Typically, the measurement distally of a stenosis (or distal in the coronary artery if no stenosis is present) is performed with a sensor-tipped guidewire. Such sensors are readily available, e.g. the PressureWire™ X Guidewire sold by the company Abbott. The pressure proximally can be measured with a so-called pressure catheter or guiding catheter. It is, however, possible to also measure the proximal pressure with a sensor-tipped guidewire. Here it should be noted that from experience it is known that aortic pressure is generally independent of the state of the patient (i.e. whether the patient is in a state of hyperemia or in rest) if blood flow, both at rest and at hyperemia, is measured by thermodilution flow measurements and saline is continuously infused at different infusion rates. Thus, according to the present invention, the proximal pressure can be measured then during rest condition of the patient or during hyperemic state of the patient. Thus, equation (3) derived above can be generalized as:

[00015]$\begin{array}{cc}\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,\mathrm{hyper}}}& \left(3b\right)\end{array}$

[0088] In case that P.sub.a does change between the state of rest and the state of hyperemia (as can be the case with other means to induce hyperemia such as—but not limited to—adenosine injection or infusion), it is important that the pressure measured proximally of the stenosis should be taken as P.sub.a at rest (also called P.sub.a,rest) and P.sub.d as P.sub.d during hyperemia (also called P.sub.d,hyper), see equation (3).The skilled person is further very familiar with methods for inducing a hyperemic state in a patient.

[0089] The flow measurements and the corresponding flow measurement system(s) for performing such flow measurements can, for example, by done with a system for measuring blood flow according to the continuous thermodilution technique. This is a technique well known to the skilled person, and is, for example, described in the U.S. Pat. No. 7,775,988 to Pijls. A catheter for such flow measurements is also readily available, for example the RayFlow™ multipurpose infusion catheter sold by the company HexaCath.

[0090] However, the skilled person knows many other techniques for invasive or non-invasive blood flow measurements. Such invasive techniques encompass bolus thermodilution, timed venous collection, electromagnetic flow measurement, conductance measurements, Doppler ultrasound, or calibrated Doppler probes, thermo-convection, thermo-conduction, and epicardial ultrasonic flow velocity measurement. Most of these techniques are, for example, described in “Maximal Myocardial Perfusion as a Measure of the Functional Significance of Coronary Artery Disease”, by N. H. J. Pijls (1991), Cip-Gegevens Koninklijke Bibliotheek, den Haag, (ISBN 90-9003818-3). Examples of non-invasive flow measurement are techniques using Computed Tomography, Magnetic Resonance Imaging, Positron Emission Tomography, or echocardiography

[0091] Typically, the system for blood flow measurement during rest condition of the patient is the same as the system for blood flow measurement during a hyperemic state of the patient. It is, however, within the scope of the invention, that a first blood flow measuring system, which is used for blood flow measurement during rest condition, is different from a second blood flow measuring system, which is used for blood flow measurements during hyperemic condition. It is also within the scope of the invention that Q.sub.max and Q.sub.rest and P.sub.a and P.sub.d can be measured at different times.

[0092] FIG. 3 shows a flow chart of an embodiment of the method according to the third aspect of the invention, which method is an alternative method of determining MRR, but will result in, at least theoretically, identical values of MRR as the method according to the first aspect of the invention. This is understood by re-arranging equation (3) as follows:

P.sub.a,rest/P.sub.d,hyper=(P.sub.a,rest/P.sub.a,hyper).Math.(P.sub.a,hyper/P.sub.d,hyper)

One gets: MRR=Q.sub.max/Q.sub.rest×(P.sub.a,rest/P.sub.a,hyper).Math.(P.sub.a,hyper/P.sub.d,hyper) [0093] Which equation makes clear that MRR contains a term (P.sub.a, rest/P.sub.a, hyper) to compensate for changes in driving pressure P.sub.a between the resting and hyperemic measurement and contains a term (P.sub.a, hyper/P.sub.d, hyper=1/FFR) to compensate for presence of any kind of epicardial disease.

[0094] This can be re-written then as:

MRR=(CFR/FFR).Math.(P.sub.a,rest/P.sub.a,hyper)  (4)

[0095] or simply MRR=(CFR/FFR) if P.sub.a remains constant between resting conditions and hyperemia. Equation (4) gives the mutual relationship between MRR, CFR and FFR and is universally valid in coronary physiology. Furthermore, equation (4) is not dependent on the technique used to obtain CFR and FFR.

[0096] The method in FIG. 3 comprises the determining 11 a value of Coronary Flow Reserve, CFR, of the coronary artery of the patient, determining 12 a value of Fractional Flow Reserve, FFR, of the coronary artery of the patient, determining 13 a value of blood pressure during rest condition of the patient, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present, determining 14 a value of blood pressure during maximum hyperemia of the patient, P.sub.a, hyper, at a position proximal in the coronary artery or proximally of any stenosis if present. The microvascular resistance reserve, MRR, is determined by the additional step of calculating 15 the microvascular resistance reserve according to equation (4).

[0097] FIG. 4 shows a flow chart of an embodiment of the method according to the third aspect of the invention. The method relates to determining microvascular resistance as defined in equation (2). The method comprises, during rest condition of the patient, measuring 21 blood flow, Q.sub.rest, through the coronary artery, and measuring 22 blood pressure, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present. The microvascular resistance at rest condition is calculated 23 as R.sub.micro,rest=P.sub.a, rest/Q.sub.rest.

[0098] FIG. 5 illustrates schematically a system according to the second aspect of the invention. The system comprises a processing unit 31 and a measuring system 32/33/34/35 using the continuous thermodilution principle. The measuring system comprises a control unit 30a, guide catheter 30b, infusion catheter 30c and a sensor 30d arranged on a sensor guide wire. As noted above, such a system is known in the art and will not be described in further detail here. The sensor 30d is configured to measure temperature and pressure. In the shown position, the measuring system can measure Q.sub.rest, Q.sub.max, P.sub.d,hyper, and by repositioning the sensor to a proximal position, Pa can be measured as well. The measuring system thus constitutes the first and second flow measuring systems as well as the first and second pressure measuring instruments in the sense of the second aspect of the invention. In other embodiments, P.sub.a may however be measured by means of a separate measuring device (such as a guide catheter), or different type(s) of measuring system(s) may be used altogether. The control unit 30a is electrically connected to the processing unit 31 via its interface 31′, such that the processing unit can obtaining blood flow measurements Q.sub.rest, Q.sub.max and blood pressure measurements P.sub.a, P.sub.d from the measuring system. The processing unit 31 is configured for calculating the microvascular resistance reserve as

[00016]$\mathrm{MRR}=\frac{Q_{\max }}{Q_{\mathrm{rest}}}\frac{P_a}{P_{d,\mathrm{hyper}}}.$

In this embodiment, the system comprises a display unit 36 which is electrically connected to the processing unit 31 and on which the measured and/or calculated values MRR, Q.sub.rest, Q.sub.max and/or P.sub.a, P.sub.d can be displayed in, preferably, real time.

[0099] FIG. 6 illustrates schematically a system according to the fifth aspect of the invention. The system comprises a processing unit 41 and an interface 42. The processing unit is configured to, in response to at least one signal received via said interface comprising data indicative of the Coronary Flow Reserve, CFR, and the Fractional Flow Reserve, FFR, of the coronary artery of the patient, of the, of the coronary artery of the patient, and further indicative of the blood pressure, P.sub.a, rest, during rest condition of the patient at a position proximal in the coronary artery or proximally of any stenosis if present, and of the blood pressure, P.sub.a, hyper, during maximum hyperemia of the patient at a position proximal in the coronary artery or proximally of any stenosis if present, determine the microvascular resistance reserve as

[00017]$\mathrm{MRR}=\frac{\mathrm{CFR}}{\mathrm{FFR}}\frac{P_{a.\mathrm{rest}}}{P_{d,\mathrm{hyper}}}.$

The system comprises a display unit 56 which is electrically connected to the processing unit 41 and on which the values of MRR, CFR and/or FFR may be displayed in, preferably, real time. A CT system 47 and a pressure measurement device 48 (a sphygmomanometer) is connected to the interface to provide data for determining CFR, FFR and MRR. The system may in other embodiments comprise a measuring system as shown in FIG. 5 connected to the interface 42. In yet other embodiments, a data storage device comprising stored values of CFR, FFR, P.sub.a, rest P.sub.a, hyper may be connected to the interface.

[0100] FIG. 7 illustrates schematically a system according to the sixth aspect of the invention. The system comprises a processing unit 51 and a thereto connected interface 52, wherein said processing unit is configured to, in response to at least one signal received via said interface comprising data indicative of the blood flow, Q.sub.rest, through the coronary artery during rest condition of the patient and of the blood pressure, P.sub.a, rest, at a position proximal in the coronary artery or proximally of any stenosis if present during rest condition of the patient, determine the microvascular resistance at rest condition as R.sub.micro,rest=P.sub.a, rest/Q.sub.rest. A CT system 57 and a pressure measurement device 58 (a sphygmomanometer) is connected to the interface to provide data indicative of Q.sub.rest, and P.sub.a, rest. In this embodiment, no display is provided. Instead, an optional wireless communications module is shown connected to the processing unit to communicate the calculated microvascular resistance. The processing unit configured to calculate R.sub.micro,rest may in other embodiments be part of the CT system. In other embodiments, the system 57 may be a PET or MRI system.

[0101] As described above, the systems according to the invention comprise a processing unit, which may obtains signals or other quantities from for example the first and second flow measuring systems and the first and second pressure measuring instruments, respectively, and which transforms these signals or other quantities into value(s) or number(s), which can be at least temporarily stored and used to calculate the resting and minimal microvascular resistance and the microvascular resistance reserve (MRR) in accordance with the invention. According to embodiments, the systems comprise a display unit, on which the measured and/or calculated values can be displayed in, preferably, real time.

[0102] As said, embodiments of the invention described above comprise a processing unit, in which processes are performed in at least one processor, the invention also extends to computer programs, particularly computer programs on or in a carrier, adapted for putting the invention into practice. The programs may be in the form of source code, object code, a code intermediate source and object code such as in partially compiled form, comprise software or firmware, or in any other form suitable for use in the implementation of the process according to the invention. The program may either be a part of an operating system, or be a separate application. The carrier may be any entity or device capable of carrying the program. For example, the carrier may comprise a storage medium, such as a Flash memory, a ROM (Read Only Memory), for example a DVD (Digital Video/Versatile Disk), a CD (Compact Disc) or a semiconductor ROM, an EPROM (Erasable Programmable Read-Only Memory), an EEPROM (Electrically Erasable Programmable Read-only Memory), or a magnetic recording medium, for example a floppy disc or hard disc. Further, the carrier may be a transmissible carrier such as an electrical or optical signal which may be conveyed via electrical or optical cable or by radio or by other means. When the program is embodied in a signal which may be conveyed directly by a cable or other device or means, the carrier may be constituted by such cable or device or means. Alternatively, the carrier may be an integrated circuit in which the program is embedded, the integrated circuit being adapted for performing, or for use in the performance of, the relevant processes. In one or more embodiments, there may be provided a computer program loadable into a memory communicatively connected or coupled to at least one data processor, e.g. the processing unit, comprising software or hardware for executing the method according any of the embodiments herein when the program is run on the at least one data processor. In one or more further embodiment, there may be provided a processor-readable medium, having a program recorded thereon, where the program is to make at least one data processor, e.g. the processing unit, execute the method according to of any of the embodiments herein when the program is loaded into the at least one data processor.

[0103] Although the present invention has been described with reference to specific embodiments, also shown in the appended drawings, it will be apparent to those skilled in the art that many variations and modifications can be done within the scope of the invention as described in the specification and defined with reference to the claims below.