Intravascular pressure and flow monitoring methods

Abstract

To provide methods for monitoring the intravascular pressure and flow.SOLUTION: An intravascular pressure and flow monitoring method includes: measuring multiple intravascular blood flow values, multiple proximal pressure values and multiple distal pressure values using one or more sensors during each of multiple cardiac cycles; determining multiple flow thresholds including a flow threshold for each of the multiple cardiac cycles using the multiple intravascular blood flow values; determining a proximal pressure value (Pa) and a distal pressure value (Pd) at the time of each flow threshold; calculating a first diagnostic parameter based upon the Pa and Pd values at the time of each flow threshold; displaying, on a user display, the diagnostic parameter for the multiple cardiac cycles.SELECTED DRAWING: Figure 1A

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 61 / 975,424, filed April 4, 2014, and U.S. Provisional Patent Application No. 62 / 073,284, filed October 31, 2014, the disclosures of which are incorporated herein by reference in their entireties.

[0002] The present disclosure relates generally to methods and apparatus for intravascular measurements, such as pressure, temperature, flow measurements, and related diagnostics. [Background technology]

[0003] The sensor and guidewire assemblies can be used to collect intravascular data with a measurement sensor located at or near the distal end of the assembly. These devices are typically used in applications to measure internal properties of tissues or fluids, such as blood pressure. The sensor and guidewire assemblies can be introduced into arteries, veins, or other body organs, either alone or through a catheter already in place in the patient. These assemblies can be used to measure pressure and other parameters.

[0004] For example, such an assembly can be used in conjunction with one or more pressure sensing devices, such as a delivery catheter, to measure fractional flow reserve (FFR) using pressure data. Additionally, coronary flow reserve (CFR) can be measured using thermodilution-based techniques. In such techniques, CFR values ​​are obtained by injecting a cold saline solution into the coronary artery of interest and using a temperature sensor to measure the time from the start of injection of cold saline into the artery until the temperature returns to a specified level.

[0005] Thermodilution has several limitations. The stated accuracy of this method is as low as ±30%. Furthermore, the procedure is laborious and time consuming, requiring multiple injections of saline with specific properties to generate enough data for the system software to calculate the CFR value. Measurement of FFR and CFR is performed as two separate methods, taking into account the nature of the required thermodilution system, saline delivery, and subsequent measurements.

[0006] FFR is used to provide a measure of the severity of coronary artery narrowing. The typical method for determining FFR is to measure the pressure drop in the coronary arteries during hyperemia. An increase in blood flow in the coronary system is induced for a controlled period of time by injecting a substance that induces hyperemia. The pressure drop is measured during this period and is used as an input in determining the FFR.

[0007] The present disclosure relates in part to methods, systems, and devices suitable for measuring FFR, CFR, and other values ​​and generating diagnostic outputs that overcome some of the challenges in existing methods. Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention is directed to solving the problems of the background art. [Means for solving the problem]

[0009] The present disclosure relates in part to methods, systems, and devices for performing intravascular pressure measurements while simultaneously measuring blood flow values, or parameters associated with such flow. These embodiments may be based on hot film or hot wire anemometry. Hot film or hot wire anemometry is a method for measuring the cooling effect of a fluid (or gas) flowing over a heated surface. When using the sensor as a hot film anemometer, the sensor is heated by an electric current, and the cooling effect of the blood flow is measured by sampling the voltage across a resistor. The voltage across the resistor may be measured along with other resistances, currents, electrical parameters, and electrical signals. These measurements can be correlated to flow parameters. In one embodiment, the voltage can be used for two related anemometry methods: constant temperature anemometry (CTA) and constant excitation voltage (CVEX) anemometry.

[0010] In one embodiment, a semiconductor-based sensor including a first temperature sensitive resistor and a second temperature sensitive resistor is used as part of a pressure sensing intravascular device. Moreover, at least one of the first and second resistors is also pressure sensitive. The sensor may be delivered over a guidewire and may be used to measure pressure across a potential stenosis while simultaneously acquiring flow, pressure, or temperature data based on changes in excitation voltage, current, temperature, or other sensor parameters. Various control systems and calibration methods may be used to assist in such pressure and flow measurements.

[0011] In one embodiment, the present disclosure relates to using a digital control system while performing simultaneous pressure and flow measurements using semiconductor based pressure sensors. Digital control systems overcome some of the deficiencies of analog control systems. In particular, some advantages of digital control systems include calibration capabilities and user specified temperature selection capabilities. Digital systems can also be used to improve the relative signal level to noise level. The calibration function involves reading information digitally encoded on a memory device associated with a given sensing probe and adjusting each stage of the control system in response to the reading. The memory device can be attached to the probe and can be, for example, a PROM, EEPROM, RFID, or other suitable memory storage device.

[0012] The temperature selection function involves automatically obtaining the temperature of the blood vessel using one or more sensors and then modifying an electrical characteristic of the sensing system. This modification to current, voltage, impedance, or another parameter is made in response to a user-specified temperature (e.g., an excess temperature or a sensed temperature range) above the temperature of the flowing blood. The excess temperature or sensed temperature range provides a range or value that can be reduced by cooling. This reduction in temperature can be measured as a result of blood flow. Alternatively, how much an electrical characteristic such as voltage or current needs to be increased to keep the excess temperature or sensed temperature range constant can be measured and correlated to blood flow. Thus, the excess temperature can be a constant or a range that changes in response to cooling.

[0013] In one embodiment, the present disclosure relates to a graphical user interface and a probe interface or a processing system or a display system or an integrated cardiology display system (ICD) (each separate or together, collectively referred to as a "measurement system") in electronic communication with a guidewire-based probe that simultaneously relays pressure data and flow data related to the pressure data. In one embodiment, suitable measurement systems, such as ICDs, may include, but are not limited to, the RadiAnalyzer system, the RadiAnalyzer Xpress system, the Quantien system, the Aeris system, the Prestige guidewire-based probe system, the ComboMap® pressure and flow system, and other devices and systems that sense intravascular pressure or determine FFR. In one embodiment, the measurement system and the probe interface or processing system and display system are the same device or collection of devices.

[0014] In one embodiment, the interface device receives signals from a guidewire-based probe representative of flow and pressure at one or more locations along a blood vessel. A guidewire-based probe sensor is placed in the catheter prior to introduction into the blood vessel. Additionally, the system obtains a zero flow reference from inside the catheter prior to introduction into the lumen of the blood vessel. This zero flow reference may be used as an input during calibration of the guidewire-based probe. Atmospheric pressure may also be used as a zero point during sensor calibration.

[0015] The timing of data collection and selection of the controlled environment in which the data is collected determines the zero or origin point against which other flow and / or pressure measurements are evaluated. The zero or calibration point can be used along with other parameters and transfer functions to convert the guidewire-based probe signal data into flow data suitable for display and analysis using one or more processors in the measurement system.

[0016] In one embodiment, the transfer function T(x) is of the form T(x)=a+b×ln(x), where T(x) provides a temperature value in response to a flow value x. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×ln(x), where T(x) provides an excitation voltage or power value in response to a flow value x. The flow value x, in one embodiment, is a flow velocity. In another embodiment, the flow value x is a flow rate. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×x^c.

[0017] In one embodiment, the transfer function is determined based on data fitting. Specifically, data used to perform such fitting may include flow rate vs. temperature, flow rate vs. excitation voltage, flow rate vs. temperature, flow rate vs. excitation voltage, etc. One or more sensor-specific parameters usable by the transfer function are stored in a memory storage device of the guidewire-based probe. In one embodiment, the transfer function is determined based on models, constraints, and other formulas alone or in combination with the data.

[0018] The time range for collecting data from the blood vessel and displaying pressure and flow information based on the collected data is from greater than about 0 seconds to about 1 second. In one embodiment, the data includes a time-varying electrical signal correlated with resistance changes. In one embodiment, the data includes a time-varying electrical signal correlated with current changes.

[0019] In one embodiment, the range of potential difference applied across one or more resistors disposed within the sensing portion of the guidewire-based probe is from greater than about 0.1 volts to about 15 volts. In one embodiment, the range of temperature changes measured within a blood vessel using the temperature (P), flow (Q), or temperature (T) sensing portion of the guidewire-based probe is from greater than about 0° C. to about 5° C. In one embodiment, the excitation voltage required to generate sufficient excess temperature (i.e., sensitivity to flow changes) is greater than about 4 volts. This excitation voltage range, in one embodiment, applies to CVEX and CTA implementations.

[0020] The disclosure relates in part to a method for collecting blood vessel related data, the method including storing guidewire-based probe data in one or more memory devices, measuring a first electrical signal associated with a first resistor and a second resistor disposed in the blood vessel, measuring a second electrical signal associated with a second resistor disposed in the blood vessel, determining a transfer function using the guidewire-based probe data, the transfer function having a flow parameter as an output, determining a blood pressure value for the blood vessel using one or more of the first and second electrical signals, determining a blood temperature value for the blood vessel using one or more of the first and second electrical signals, determining a blood flow value for the blood vessel using one or more of the first and second electrical signals and the transfer function, and displaying a pressure vs. flow curve for the blood vessel. In one embodiment, the transfer function relates to the flow parameter and an excitation voltage. In one embodiment, the transfer function relates to the flow value and the temperature of one or more of the first and second resistors. In one embodiment, the method further includes identifying occurrences of one or more of maximum flow rates, minimum flow rates, and relative extremes of flow rates, and correlating such occurrences with intravascular or cardiac events.

[0021] The present disclosure relates in part to an intravascular pressure and flow monitoring system that includes one or more memory devices and a computing device in communication with the memory device, the memory device including instructions executable by the computing device to cause the computing device to determine one or more intravascular pressure values ​​in response to a first electrical signal from a measurement circuit formed from the guidewire-based probe and an interface device, determine one or more intravascular flow values ​​using a transfer function in response to a second electrical signal from the measurement circuit formed from the guidewire-based probe and an interface device, and display a time-varying pressure vs. flow curve generated based on the one or more intravascular pressure and intravascular flow values.

[0022] In one embodiment, the pressure vs. flow curve is displayed in near real time. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×ln(x), where x is the flow rate and a and b are constants. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×ln(x), where x is the flow rate and a and b are constants. c where x is the flow rate and a, b, and c are constants. In one embodiment, the system further includes instructions for displaying one or more cardiovascular-related values ​​obtained during one or more time points.

[0023] In one embodiment, the one or more cardiovascular-related values ​​are selected from the group consisting of flow velocity, pressure values, maximum flow rates, minimum flow rates, relative extreme values ​​of flow rates, one or more Fractional Flow Reserve (FFR) values, Coronary Flow Reserve (CFR) values, Coronary Flow Velocity Reserve (CFVR) values, Instantaneous Flow Reserve (IFR) values, and one or more Index of Myocardial Resistance (IMR) values.

[0024] In one embodiment, the system further includes instructions for displaying one or more trajectories or signatures generated in response to the intravascular probe data for one or more locations within the artery. In one embodiment, the system further includes instructions for displaying a user interface including flow velocity, pressure values, maximum flow rates, minimum flow rates, relative extremes of flow rates, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, or one or more myocardial resistance index (IMR) values ​​generated using the pressure and flow data from the intravascular probe.

[0025] In one embodiment, the system further includes instructions for determining one or more temperature values ​​using a linear or other function in response to a second electrical signal from a measurement circuit formed from the guide wire-based probe and the interface device.

[0026] The present disclosure relates in part to an intravascular pressure and flow monitoring adapter kit. The kit includes a power supply, the power supply including a first intravascular pressure measurement system output connection and a second intravascular pressure measurement system output connection, the power supply having a power output range of greater than about 0.2 volts to less than about 12 volts, and the power supply sized to electrically connect with the intravascular pressure measurement system. The kit may include one or more electrical components in electrical communication with the power supply. In one embodiment of the kit, the one or more electrical components are selected from the group consisting of a filter, an amplifier, a current source, a voltage source, and a control system connection.

[0027] In one embodiment of the kit, the power output range is from about 0.3 volts to less than about 30 volts. In one embodiment of the kit, the kit further includes a non-transient storage medium containing instructions for causing a computing device of the intravascular pressure monitoring system to store in memory a transfer function that outputs an intravascular flow value in response to an excitation voltage or temperature, and to generate an intravascular flow value in response to (i) an excitation voltage from the power supply and the transfer function, or (ii) a difference between a fixed voltage and a voltage across a temperature dependent resistor.

[0028] The disclosure relates in part to a method for calibrating a flow monitoring device, the method including the steps of selecting an excitation voltage for a pressure sensor such that a temperature of the pressure sensor substantially matches a temperature of blood in which the pressure sensor is disposed, determining an absolute temperature of the blood in a blood vessel of interest, and using the pressure sensor to measure a flow value in the blood vessel. In one embodiment, the method includes the step of determining the absolute temperature of the blood in the blood vessel of interest including taking measurements during a change in a switch configuration in an interface system.

[0029] The present disclosure relates in part to an integrated cardiology system including a display system, a pressure and flow measurement system in electrical communication with the display system, a processor disposed in one of the display system or the pressure and flow measurement system, and one or more panels generated using the processor and depicted on the display, the one or more panels including flow and pressure values ​​obtained using an intravascular probe including a pressure and flow sensor. In one embodiment, the one or more panels include a pressure vs. flow curve, the pressure vs. flow curve including one or more trajectories generated using the intravascular pressure and flow data, and further includes an input for receiving a data signal from the intravascular probe, the intravascular probe including a temperature sensor for measuring temperature changes correlated with the flow values.

[0030] In one embodiment, the trajectory may include, but is not limited to, a graphical representation of transitions between states associated with the cardiac cycle and may change in response to stenosis, pressure changes in the artery, and flow changes due to contraction or other arterial or cardiac conditions. In one embodiment, one or more panels include a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of a measurement, a ratio of a measurement to a derived value, a ratio of a first derivative to a second derivative, a range, one or more of a fractional flow reserve (FFR) value, a coronary flow reserve (CFR) value, a coronary flow velocity reserve (CFVR) value, an instantaneous flow reserve (IFR) value, and one or more myocardial resistance index (IMR) values.

[0031] The present disclosure relates in part to an intravascular pressure and flow monitoring system that includes an intravascular pressure and flow interface system including a wired or wireless interface for receiving data from an intravascular probe, a display system in electrical communication with the intravascular pressure and flow interface system, one or more memory storage devices containing instructions for outputting a user interface on the display including one or more panels having fields for one or more flow measurements, and a processor in electrical communication with the intravascular pressure and flow interface system, the display system, and the one or more memory storage devices, the processor responsive to the instructions to output the user interface on the display system.

[0032] In one embodiment, the system includes a calibration system configured to convert one of the measured temperature signal or the excitation voltage to a flow velocity using a transfer function. In one embodiment, the transfer function is a+b×lnx and / or a+b×x c In one embodiment, the display system outputs measurements of pressure and flow velocity simultaneously. In one embodiment, the display system outputs measurements of pressure and absolute temperature simultaneously. In one embodiment, the display system outputs one or more parameters or indices corresponding to one or more signals acquired at the measurement location of the probe sensor.

[0033] In one embodiment, the one or more parameters or indices are selected from the group consisting of a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of a measurement, a ratio of a measurement to a derived value, a ratio of a first derived value to a second derived value, a range, a fractional flow reserve (FFR) value, a coronary flow reserve (CFR) value, a coronary flow velocity reserve (CFVR) value, an instantaneous flow reserve (IFR) value, and one or more myocardial resistance index (IMR) values. In one embodiment, the wired interface includes an excitation voltage source, a first resistor, a second resistor, a first switch, and a second switch. In one embodiment, the wireless interface includes a plurality of current sources, a plurality of switches, a first resistor, and a second resistor, each current source in series with one of the switches. Coronary Flow Reserve Related Features and Embodiments

[0034] The present disclosure relates, in part, to methods and systems suitable for determining one or more coronary flow reserve (CFR) and fractional flow reserve (FFR) values, separately or simultaneously, using thermal convection devices, such as intravascular pressure and flow sensors, and an intravascular data acquisition and processing system. Additionally, the present disclosure also relates, in part, to determining CFR values ​​using an intravascular probe having a pressure sensor and constant temperature anemometry (CTA) or constant voltage excitation (CVEX) anemometry.

[0035] The present disclosure also relates to a method of determining coronary flow reserve data using an intravascular pressure or flow sensor, the method including the steps of sampling an intravascular data collection probe to obtain one or more distal pressure values ​​(Pd) from a distal region of a blood vessel and one or more thermal convection data values, receiving one or more aortic pressure values ​​(Pa) obtained from a proximal region of the blood vessel at an intravascular data processing system, determining one or more fractional flow reserve (FFR) values ​​from the one or more distal pressure values ​​and the one or more aortic pressure values, determining one or more coronary flow reserve (CFR) values ​​from the one or more thermal convection data values, and displaying the one or more FFR values ​​and the one or more CFR values ​​on a display device.

[0036] In one embodiment, each CFR value is determined using a transfer function. In one embodiment, the transfer function is of the form T=a+c×lnQ, where T is the measured temperature of a temperature variable resistor of the heat convection device, Q is the flow rate, and a and c are constants. In one embodiment, the step of determining one or more coronary flow reserve (CFR) values ​​is performed using the measured temperature T hyp and the measured temperature at the baseline flow rate, T bas In one embodiment, each CFR value is of the form b

number

[0037] The present disclosure relates, in part, to a data collection method and / or diagnostic method using collected data, e.g., measured pressure, temperature, or flow values, including setting a zero value for a distal pressure signal measured by an intravascular heat convection device, placing the intravascular heat convection device at an opening of a delivery catheter, setting a zero value for a temperature signal measured by the intravascular heat convection device prior to advancement within the vasculature, advancing the intravascular heat convection device to a position distal to the catheter opening, equalizing the intravascular heat convection device pressure (Pd) signal to an aortic pressure (Pa) signal, adjusting or optimizing the intravascular heat convection device temperature signal when the intravascular heat convection device is at the measurement location of interest, sampling the intravascular heat convection device to obtain a baseline heat convection signal value, and sampling the intravascular heat convection device to obtain Pd and heat convection device values ​​for performing FFR and CFR calculations. In one embodiment, the method further includes verifying that the pressures have been equalized and that the flow signal has returned to a baseline level. In one embodiment, the method further includes displaying the one or more FFR values ​​and the one or more CFR values ​​relative to a graphical user interface including one or more axes and one or more control inputs. In one embodiment, the control inputs and the user interface are implemented using a touch screen.

[0038] The present disclosure relates in part to an intravascular data monitoring system including an intravascular data collection system including an interface for receiving data from an intravascular probe, a display system in electrical communication with the intravascular data collection system, one or more memory storage devices including instructions for outputting a user interface on the display system, the user interface including one or more regions for displaying one or more CFR values ​​or plots thereof, the user interface including one or more regions for displaying one or more FFR values ​​or plots thereof, and a processor in electrical communication with the intravascular data collection system, the display system, and the one or more memory storage devices, the processor being programmed to: sample a plurality of proximal pressure values ​​(Pa), sample a plurality of distal pressure values ​​(Pd), sample a plurality of thermal convection data values, and use the sampled Pa, Pd, and thermal convection data values ​​to determine one or more CFR values ​​and one or more FFR values.

[0039] The present disclosure relates in part to a method for calibrating an intravascular data collection system, the method including the steps of: establishing a baseline value for a distal pressure signal measured by an intravascular heat convection device, placing the intravascular heat convection device at an opening of a delivery catheter, establishing a baseline value for a temperature signal measured by the intravascular heat convection device prior to advancement through the vasculature, advancing the intravascular heat convection device to a position distal to the catheter opening, equalizing the intravascular heat convection device pressure (Pd) signal to an aortic pressure (Pa) signal, calibrating the intravascular heat convection device temperature signal when the intravascular heat convection device is at a measurement location of interest, and sampling the intravascular heat convection device to obtain a Pd value and a heat convection device value. Stenosis assessment and flow threshold / flow peak guided measurement embodiments

[0040] The present disclosure relates in part to an intravascular pressure monitoring system and data collection device suitable for analyzing pressure drops under non-hyperemic or hyperemic conditions, identifying one or more flow thresholds, and collecting or otherwise generating diagnostic data referenced to data collected at such selected time points. In one embodiment, pressure ratios, such as distal to proximal ratios, or pressure differences are collected at one or more various flow thresholds over time. Using the pressure and flow values ​​measured at each flow threshold, an arithmetic mean of the pressure ratio / pressure difference over several heartbeats can be calculated.

[0041] The present disclosure relates in part to a method for evaluating a blood vessel, the method including the steps of measuring a plurality of intravascular blood flow values ​​and a plurality of blood pressure values ​​over one or more heartbeats using one or more sensors, determining a flow threshold over one or more heartbeats using one or more of the plurality of intravascular blood flow values, determining a proximal pressure value (Pa) and a distal pressure value (Pd) between the flow thresholds, calculating a first diagnostic parameter based on the Pa and Pd values ​​at the flow threshold over one or more heartbeats, and displaying the first diagnostic parameter over one or more heartbeats or a second diagnostic parameter determined using the first diagnostic parameter on a user display. In one embodiment, the first diagnostic parameter is a pressure difference Pa-Pd or a pressure ratio Pd / Pa. In one embodiment, the plurality of blood pressure values ​​include one or more proximal pressure values ​​measured relative to a stenosis and one or more aortic pressure values.

[0042] In one embodiment, the first diagnostic parameter and the second diagnostic parameter are selected from the group consisting of Pa, Pd, Pd / Pa, Pa-Pd, flow velocity, pressure value, maximum flow rate, minimum flow rate, relative extremes of flow rate, fractional flow reserve (FFR) value, coronary flow reserve (CFR) value, coronary flow velocity reserve (CFVR) value, instantaneous flow reserve (IFR) value, and one or more index of myocardial resistance (IMR) values. In one embodiment, the flow threshold is selected from the group consisting of maximum flow rate during a cardiac cycle, relative extremes of flow rate during a cardiac cycle, a fraction of the maximum flow rate during a cardiac cycle, maximum flow rate during hyperemia, and flow rate during non-hyperemia.

[0043] In one embodiment, the step of measuring a plurality of intravascular blood flow values ​​and a plurality of blood pressure values ​​further includes the steps of measuring a first electrical signal associated with a first resistor and a second resistor placed in the blood vessel, measuring a second electrical signal associated with a second resistor placed in the blood vessel, determining one or more blood pressure values ​​of the plurality of intravascular blood pressure values ​​using one or more of the first and second electrical signals, determining one or more blood temperature values ​​of the blood vessel using one or more of the first and second electrical signals, and determining a plurality of intravascular blood flow values ​​of the blood vessel using one or more of the first and second electrical signals.

[0044] In one embodiment, one or more of the blood pressure values ​​are aortic pressure values ​​or proximal pressure values. In one embodiment, the first diagnostic parameter is a plot of values ​​against time. In one embodiment, the step of calculating the first diagnostic parameter includes calculating an average value of a pressure ratio or pressure difference over multiple cardiac cycles according to a flow threshold determined for each cardiac cycle. In one embodiment, the first diagnostic parameter is an average value of a pressure ratio over multiple cardiac cycles or an average value of a pressure difference over multiple cardiac cycles.

[0045] The disclosure relates in part to a method for evaluating a blood vessel, the method including the steps of receiving vascular blood flow and blood pressure data acquired during one or more cardiac cycles, the vascular blood flow data including a peak blood flow value, determining a flow threshold including the peak blood flow value, determining a first vascular blood pressure (Pa) and a second vascular blood pressure (Pd) at the peak blood flow in each of one or more cardiac cycles, calculating one or more pressure differences between Pa and Pd in ​​each of one or more cardiac cycles, or one or more pressure ratios Pd / Pa in each of one or more cardiac cycles, and displaying diagnostic information about the blood vessel on a user display, the diagnostic information including one or more of a pressure ratio, a pressure difference, or a plot thereof. In one embodiment, the step of calculating the pressure difference includes calculating an average of the pressure difference over multiple cardiac cycles.

[0046] In one embodiment, the method further includes receiving an electrical signal correlated with a temperature change of an intravascular heat convection device in thermal communication with a blood vessel, the temperature change correlated with a change in flow over one or more cardiac cycles, the intravascular blood flow data including the electrical signal, and determining a peak blood flow value from the electrical signal correlated with the temperature change.

[0047] In one embodiment, the method further includes receiving an electrical signal correlated with a temperature change of an intravascular heat convection device in thermal communication with a blood vessel, the temperature change correlated with a change in flow over one or more cardiac cycles, the intravascular blood flow data including the electrical signal, and determining a peak blood flow value from the electrical signal correlated with the temperature change. Other embodiments and implementations

[0048] The present disclosure relates in part to an intravascular pressure and flow monitoring system. The system includes one or more memory devices and a computing device in communication with the memory device, the memory device including instructions executable by the computing device to cause the computing device to determine one or more intravascular pressure values ​​in response to a first electrical signal from a measurement circuit formed from the guidewire-based probe and an interface device, determine one or more intravascular flow values ​​using a transfer function in response to a second electrical signal from the measurement circuit formed from the guidewire-based probe and the interface device, and display a time-varying pressure vs. flow curve generated based on the one or more intravascular pressure and intravascular flow values. In one embodiment, the pressure vs. flow curve is displayed in near real time. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×ln(x), where x is the flow rate, and a and b are constants. In one embodiment, the transfer function T(x) is of the form T(x)=a+b×x c where x is the flow rate and a, b, and c are constants.

[0049] In one embodiment, the system further includes instructions for displaying one or more cardiovascular-related values ​​obtained during the one or more time points, in one embodiment, the one or more cardiovascular-related values ​​are selected from the group consisting of flow velocity, pressure value, maximum flow rate, minimum flow rate, relative extremes of flow rate, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, and one or more myocardial resistance index (IMR) values.

[0050] In one embodiment, the system further includes instructions for displaying one or more trajectories or signatures generated in response to the intravascular probe data for one or more locations within the artery. In one embodiment, the system further includes instructions for displaying a user interface including flow velocity, pressure values, maximum flow rates, minimum flow rates, relative extremes of flow rates, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, or one or more myocardial resistance index (IMR) values ​​generated using the pressure and flow data from the intravascular probe.

[0051] In one embodiment, the system further includes instructions for determining one or more temperature values ​​using a linear or other function in response to a second electrical signal from a measurement circuit formed from the guidewire-based probe and the interface device. In one embodiment, the system further includes instructions for calibrating the guidewire-based probe by the following calibration method steps: selecting an excitation voltage for the pressure sensor such that a temperature of the pressure sensor approximately matches a temperature of the blood in which the pressure sensor is disposed, determining an absolute temperature of blood in the blood vessel of interest, and measuring a flow value in the blood vessel using the pressure sensor. In one embodiment, determining the absolute temperature of blood in the blood vessel of interest includes taking measurements during a change in a switch configuration in the interface system.

[0052] In one embodiment, the intravascular pressure and flow monitoring system further includes a display system, a pressure and flow measurement system in electrical communication with the display system and including a computing device, the computing device disposed in one of the display system or the pressure and flow measurement system, and one or more panels generated using the computing device and depicted on the display, the one or more panels including flow and pressure values ​​obtained using an intravascular probe including pressure and flow sensors.

[0053] In one embodiment, the one or more panels include a pressure vs. flow curve, the pressure vs. flow curve including one or more trajectories generated using intravascular pressure and flow data, and further includes an input for receiving a data signal from an intravascular probe including a temperature sensor for measuring a temperature change correlated with the flow value. In one embodiment, the one or more panels include a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of a measurement, a ratio of a measurement to a derived value, a ratio of a first derivative to a second derivative, a range, one or more of a fractional flow reserve (FFR) value, a coronary flow reserve (CFR) value, a coronary flow velocity reserve (CFVR) value, an instantaneous flow reserve (IFR) value, and one or more myocardial resistance index (IMR) values.

[0054] In one embodiment, the intravascular pressure and flow monitoring system further includes instructions for processing coronary flow reserve data using the intravascular pressure or flow sensor, the instructions including sampling the intravascular data collection probe to obtain one or more distal pressure values ​​(Pd) from a distal region of the blood vessel and one or more heat convection data values, receiving one or more aortic pressure values ​​(Pa) obtained from a proximal region of the blood vessel at the intravascular data processing system, determining one or more fractional flow reserve (FFR) values ​​from the one or more distal pressure values ​​and the one or more aortic pressure values, determining one or more coronary flow reserve (CFR) values ​​from the one or more heat convection data values, and displaying the one or more FFR values ​​and the one or more CFR values ​​on a display device, where each CFR value is determined using a transfer function. In one embodiment, the transfer function is of the form T=a+c×lnQ, where T is the measured temperature of a temperature variable resistor of the heat convection device, Q is the flow rate, and a and c are constants. In one embodiment, each CFR value has the form b

number

[0055] The present disclosure relates in part to a method for monitoring pressure and flow in a blood vessel. The method includes the steps of measuring a plurality of intravascular blood flow values ​​and a plurality of blood pressure values ​​over one or more heartbeats using one or more sensors, determining a flow threshold over one or more heartbeats using one or more of the plurality of intravascular blood flow values, determining a proximal pressure value (Pa) and a distal pressure value (Pd) between the flow thresholds, calculating a first diagnostic parameter based on the Pa and Pd values ​​at the flow threshold over one or more heartbeats, and displaying the first diagnostic parameter over one or more heartbeats or a second diagnostic parameter determined using the first diagnostic parameter on a user display. In one embodiment, the first diagnostic parameter may be a pressure difference Pa-Pd or a pressure ratio Pd / Pa. In one embodiment, the plurality of blood pressure values ​​include one or more proximal pressure values ​​measured relative to a stenosis and one or more aortic pressure values.

[0056] In one embodiment, the first diagnostic parameter and the second diagnostic parameter are selected from the group consisting of Pa, Pd, Pd / Pa, Pa-Pd, flow velocity, pressure value, maximum flow rate, minimum flow rate, relative extremes of flow rate, fractional flow reserve (FFR) value, coronary flow reserve (CFR) value, coronary flow velocity reserve (CFVR) value, instantaneous flow reserve (IFR) value, and one or more index of myocardial resistance (IMR) values. In one embodiment, the flow threshold is selected from the group consisting of maximum flow rate during a cardiac cycle, relative extremes of flow rate during a cardiac cycle, a fraction of the maximum flow rate during a cardiac cycle, maximum flow rate during hyperemia, and flow rate during non-hyperemia. In one embodiment, the step of measuring a plurality of intravascular blood flow values ​​and a plurality of blood pressure values ​​further includes the steps of measuring a first electrical signal associated with a first resistor and a second resistor placed in the blood vessel, measuring a second electrical signal associated with a second resistor placed in the blood vessel, determining one or more blood pressure values ​​of the plurality of intravascular blood pressure values ​​using one or more of the first and second electrical signals, determining one or more blood temperature values ​​of the blood vessel using one or more of the first and second electrical signals, and determining a plurality of intravascular blood flow values ​​of the blood vessel using one or more of the first and second electrical signals.

[0057] In one embodiment, the step of calculating the first diagnostic parameter includes calculating an average value of a pressure ratio or pressure difference over multiple cardiac cycles according to a flow threshold determined for each cardiac cycle. In one embodiment, the first diagnostic parameter is an average value of the pressure ratio over multiple cardiac cycles or an average value of the pressure difference over multiple cardiac cycles. In one embodiment, the method includes receiving an electrical signal correlated with a temperature change of an intravascular heat convection device in thermal communication with a blood vessel, the temperature change correlated with a change in flow over one or more cardiac cycles, the intravascular blood flow data including the electrical signal, and determining a peak blood flow value from the electrical signal correlated with the temperature change.

[0058] In one embodiment, the method further includes the steps of calibrating the intravascular data collection system, including setting a baseline value for the distal pressure signal measured by the intravascular heat convection device; placing the intravascular heat convection device at an opening of the delivery catheter; setting a baseline value for the temperature signal measured by the intravascular heat convection device prior to advancement within the vasculature; advancing the intravascular heat convection device to a position distal to the catheter opening; equating the intravascular heat convection device pressure (Pd) signal to an aortic pressure (Pa) signal; calibrating the intravascular heat convection device temperature signal when the intravascular heat convection device is in the measurement location of interest; and sampling the intravascular heat convection device to obtain a Pd value and a heat convection device value.

[0059] The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating principles. The drawings are to be considered in all respects illustrative and are not intended to limit the disclosure, the scope of which is defined solely by the claims. [Brief description of the drawings]

[0060] [Figure 1A] FIG. 1 is a schematic diagram of an intravascular probe suitable for measuring pressure, flow parameters, and other parameters of interest in a wired configuration with one or more measurement systems. [Figure 1B] FIG. 1 is a schematic diagram of an intravascular probe suitable for measuring pressure, flow, and other parameters of interest in a wireless configuration with one or more measurement systems. [Figure 2A] 1 is a schematic diagram of a blood vessel having a guidewire-based pressure and flow sensing probe disposed therein, according to an exemplary embodiment of the present disclosure. [Figure 2B] 1 is a schematic diagram of the sensing region and associated components of an exemplary embodiment of a guidewire-based probe suitable for simultaneously measuring pressure and flow, according to an exemplary embodiment of the present disclosure. [Figure 2C]1 is an image of a portion of a semiconductor substrate of a guidewire-based probe including active and passive resistors for pressure and flow sensing according to an exemplary embodiment of the present disclosure. [Figure 2D] FIG. 2 is a perspective view of a guidewire-based probe showing a capsule surrounding a sensor array according to an exemplary embodiment of the present disclosure. [Diagram 3] FIG. 2 is a circuit diagram including various resistors and nodes as component representations of probes, connections, and their associated contact pads, according to an exemplary embodiment of the present disclosure. [Figure 4A] FIG. 2 is a circuit diagram including various resistors and nodes as a representation of components of an intravascular probe and an interface system or processing system in a bridge configuration according to an exemplary embodiment of the present disclosure. [Figure 4B] FIG. 2 is a circuit diagram including various resistors and nodes as a representation of components of an intravascular probe and an interface system or processing system in a bridge configuration according to an exemplary embodiment of the present disclosure. [Figure 5A] FIG. 4B is a schematic diagram of a signal sampling system for use with an intravascular probe and measurement bridge combination as shown in FIG. 4A. [Figure 5B] FIG. 1 is a schematic diagram of a control system for an embodiment of constant temperature anemometry (CTA) using a guidewire-based probe, according to an exemplary embodiment of the present disclosure. [Figure 5C] FIG. 1 is a schematic diagram of a constant temperature control system that monitors changes in excitation voltage, according to an exemplary embodiment of the present disclosure. [Figure 5D] FIG. 1 is a schematic diagram of a flow calculation system implemented using a constant excitation voltage (CVEX), according to an exemplary embodiment of the present disclosure. [Figure 5E] FIG. 1 is a schematic diagram of software signal processing for simultaneously measuring pressure and flow using CVEX, according to an exemplary embodiment of the present disclosure. [Figure 6A] 1A-1C are transfer function plots and representations of CTA and CVEX implementations, respectively, of pressure and flow monitoring using an intravascular probe, according to an exemplary embodiment of the present disclosure. [Figure 6B] 1A-1C are transfer function plots and representations of CTA and CVEX implementations, respectively, of pressure and flow monitoring using an intravascular probe, according to an exemplary embodiment of the present disclosure. [Figure 7A] 1 illustrates a comparison of a measured flow signal (blue) with a reference flow signal (red) in one embodiment of the present disclosure, the measurements being performed using a fictitious flow rate. [Figure 7B] Figure 1 shows a plot of flow velocity versus pullback from the distal LAD to the proximal LAD.Recordings were made in a beating, isolated porcine heart. [Figure 8A] FIG. 13 shows plots of pressure and flow versus time obtained using a pressure and flow sensing probe with a sensor placed in the proximal RCA of a pig heart, according to an exemplary embodiment of the present disclosure. [Figure 8B] FIG. 13 shows plots of pressure and flow versus time obtained using a pressure and flow sensing probe with a sensor placed in the proximal LAD of a pig heart, according to an exemplary embodiment of the present disclosure. [Figure 8C] 8D shows a plot of pressure versus flow obtained using a pressure and flow sensing probe according to an exemplary embodiment of the present disclosure, with loops or trajectories obtained for the RCA, with points corresponding to the markings shown in FIG. [Figure 8D] 8A-8C show plots of pressure and flow versus time for a flow velocity profile obtained for an RCA using a pressure and flow sensing probe according to an exemplary embodiment of the present disclosure, with points corresponding to the markings shown in FIG. [Figure 8E] 8A-8F show plots of pressure versus flow obtained using a pressure and flow sensing probe according to an exemplary embodiment of the present disclosure, with loops or trajectories obtained for the LCA, with points corresponding to the markings shown in FIG. [Figure 8F]8A-8D show plots of pressure and flow versus time for a flow velocity profile obtained for an LCA according to an exemplary embodiment of the present disclosure, with points corresponding to the markings shown in FIG. [Figure 9A] FIG. 1 illustrates a plot of pressure and flow versus time in the proximal left anterior descending coronary artery, according to an exemplary embodiment of the present disclosure. [Figure 9B] 9A-9C show plots of myocardial resistance versus time according to an exemplary embodiment of the present disclosure.The plot in Fig. 9B is obtained by dividing the pressure by the flow signal in Fig. 9A. [Figure 10A] 10A and 10B show plots of pressure versus flow (top) and pressure versus time (bottom) in a normal scenario (FIG. 10A) and an abnormal scenario (FIG. 10B), according to an exemplary embodiment of the present disclosure. The abnormal scenario shown in FIG. 10B was created by an occlusion balloon causing a myocardial infarction. [Figure 10B] 10A and 10B show plots of pressure versus flow (top) and pressure versus time (bottom) in a normal scenario (FIG. 10A) and an abnormal scenario (FIG. 10B), according to an exemplary embodiment of the present disclosure. The abnormal scenario shown in FIG. 10B was created by an occlusion balloon causing a myocardial infarction. [Figure 11] 1 is a schematic diagram of an intravascular data collection and display system suitable for measuring CFR using an intravascular sensing device, according to an exemplary embodiment of the present disclosure. [Figure 12A] 1 is a flowchart of an exemplary method of endovascular data analysis and display, according to an exemplary embodiment of the present disclosure. [Figure 12B] 1 is a flowchart of an exemplary method of endovascular data analysis and display, according to an exemplary embodiment of the present disclosure. [Figure 13A] 1 is a screen shot of an exemplary user interface and data display in review mode, according to an exemplary embodiment of the present disclosure. [Figure 13B] 1 is a screen shot of an exemplary user interface and data display in review mode, according to an exemplary embodiment of the present disclosure. [Figure 13C] 1 is a screen shot of an exemplary user interface and data display in review mode, according to an exemplary embodiment of the present disclosure. [Figure 13D] 1 is a screen shot of an exemplary user interface and data display in review mode, according to an exemplary embodiment of the present disclosure. [Figure 14] 1 is a graph showing the performance of one system according to an exemplary embodiment of the present disclosure, which is used to determine a CFR value by comparison with a reference CFR value. [Figure 15A] 1 is a screen shot of an exemplary user interface and data display according to an exemplary embodiment of the present disclosure. [Figure 15B] 1 is a screen shot of an exemplary user interface and data display according to an exemplary embodiment of the present disclosure. [Figure 15C] 1 is a screen shot of an exemplary user interface and data display according to an exemplary embodiment of the present disclosure. [Figure 15D] 1 is a screen shot of an exemplary user interface and data display according to an exemplary embodiment of the present disclosure. [Figure 16] FIG. 1 illustrates a diagnostic method associated with flow threshold detection, according to an exemplary embodiment of the present disclosure. [Figure 17A] 1 is a flow chart illustrating a method embodiment related to intravascular data collection, analysis, and display of diagnostic information of interest, according to an exemplary embodiment of the present disclosure. [Figure 17B] 1 is a flow chart illustrating a method embodiment related to intravascular data collection, analysis, and display of diagnostic information of interest, according to an exemplary embodiment of the present disclosure. [Figure 18] 1 is a plot of pressure ratios and pressure differences obtained at multiple flow thresholds obtained at various times using a sensing device versus pressure measurements (top) and measurements correlated with flow measurements / flow values ​​(bottom) in accordance with an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0061] A variety of data acquisition and analysis systems are available to obtain information about the coronary system. Data obtained from the blood vessels using the devices, or derived from their associated intravascular or extravascular measurements, can be analyzed or displayed to perform correlations and extrapolations that are useful to researchers and clinicians. For example, a variety of measurement systems and intravascular probes are available to determine the fractional flow reserve (FFR) for a blood vessel using pressure sensor-based devices. Intravascular ultrasound (IVUS) is an imaging modality that uses sound waves to image a portion of a blood vessel, while optical coherence tomography (OCT) is an imaging modality that uses an interferometer to obtain distance measurements relative to the blood vessel or objects placed within the vessel.

[0062] Intravascular data collection devices can be used within a blood vessel to generate and receive signals containing diagnostic information relative to the blood vessel. Such devices include, but are not limited to, imaging devices such as optical and ultrasound probes, pressure sensor devices, flow sensors, temperature sensors, chemical sensors such as ion sensors, and other devices suitable for collecting data about blood vessels or other components of the cardiovascular system. Also, for example, as shown in Figures 1A and 1B, a catheterization lab angiography system 95 and other external sensors 97 can be used to image the patient and provide data to the measurement system along with data from other devices and systems 10, 20 described herein.

[0063] Such devices and systems may be used to determine coronary flow reserve (CFR) and fractional flow reserve (FFR) values ​​separately or simultaneously, as described in more detail herein. Additionally, pressure ratios and pressure differentials may be selectively measured at a particular time point or points. These time points may correspond to flow thresholds, e.g., peak flow, or another flow extreme, or values ​​that correlate with or are derived from flow values ​​at times corresponding to periodic events during the cardiac cycle. One example of such a periodic event is a time point of peak or maximum flow that occurs repeatedly as the heart expands and contracts, but does not necessarily result in the same level of flow.

[0064] The present disclosure relates in part to methods, systems, and devices that allow for obtaining blood flow and pressure measurements within a blood vessel and using them to generate diagnostic feedback for a patient. References herein to obtaining blood flow measurements, measuring blood flow values ​​or flow parameters, and similar references to blood flow are references to flow velocity or correlation values, not absolute flow values. In particular, various embodiments of the disclosure described herein perform intravascular pressure measurements simultaneously while obtaining blood flow information or parameters correlated with such blood flow. Using a method based on CTA and CVEX flow velocimetry in one or more embodiments, it is possible to perform simultaneous flow and pressure measurements on a blood vessel using a single guidewire-based probe that includes one or more optical or electrical sensors. The probe may include other sensors, such as OCT, IVUS, and other data collection sensors.

[0065] In a CTA embodiment, a constant temperature is maintained across the temperature sensor. A control system is used to maintain the temperature and is capable of detecting when the voltage required to maintain the temperature changes. As a result, the cooling effect of the fluid flowing across the temperature sensor can be converted into a time-varying voltage that corresponds to a flow parameter. In contrast, in a CVEX embodiment, the excitation voltage across the temperature sensor is held constant and changes in resistance, impedance, and other voltage, current, or time-varying parameters are measured as indicative of the flow parameter.

[0066] Intravascular blood flow measurements can be used alone or in combination with other measurements to display diagnostic information of interest in real time or near real time (e.g., within a time period of about 0 to about 5 seconds). An integrated cardiology display system (ICD), which may include one or more measurement systems, can be used to display various types of patient related data acquired using intravascular probes and other catheterization lab measurement devices (e.g., angiography systems), integrated with room temperature, blood oxygen, etc. These capabilities are described in more detail further herein.

[0067] 1A and 1B show different types of guidewire-based device systems 10, 20 suitable for use in a catheterization lab environment or other environment that allows for the acquisition and display of intravascular blood flow measurements. In FIG. 1A, an intravascular probe 20 is shown that includes a wired connection 90 to an interface system 80. In contrast, in FIG. 1B, an intravascular probe 35 is shown that includes a wireless connection 91 to an interface system 82. Each device shown in FIGS. 1A and 1B includes a guidewire 40 and one or more sensors disposed at a distal end of the guidewire, which constitute components of an intravascular probe. The distal end of the guidewire is sized for insertion into a blood vessel, such as a coronary artery. The one or more sensors define a sensing region suitable for sensing or measuring one or more of a pressure value P, a flow value Q, a value correlated with flow, a temperature value T, and changes associated with any of these. A PQT sensing region 45 may correspond to the tip of the intravascular probe. The pressure sensor may be electrical, mechanical, or optical, as appropriate for a given implementation.

[0068] 1A and 1B also show close-up views of the probe tip of each type of intravascular probe, respectively. As shown in the close-up views, the guidewire 40 is adjacent to a jacket or capsule 50 or other support structure that defines a cavity above the sensor array 43. The jacket or capsule may be a metal tube in one embodiment. The sensor array may include one or more sensors. In one embodiment, the sensor array 43 includes a pressure-sensitive resistor and a temperature-sensitive resistor. In another embodiment, the sensor array includes an optical pressure sensor, for example a fiber-optic pressure sensor. The sensor array may include optical flow sensors, mechanical flow sensors, and other flow sensors. Depending on the type of pressure and flow sensor, electrical or optical connections extend from the sensor array through the guidewire to the proximal connector. The probe tip may include one or more coils 55, for example for traversability detection or angiography detection, as shown in FIG. 2D.

[0069] As shown in Figures 1A and 1B, the proximal connectors 70, 72 are different for the two types of probes 30, 35. The proximal connector 70 in Figure 1A communicates with the probe tip at its distal end and connects to a guidewire at the proximal end of the probe. As shown in Figure 1A, the proximal connector 70 connects to a probe interface / processing system 80 via a releasable wired connection 90. In contrast, the intravascular probe 35 in Figure 1B has a guidewire extending to the proximal connector 72, which includes a transmitter 75.

[0070] With reference to the wireless embodiment of Figure 1B, the transmitter wirelessly transmits signals from the probe to the probe interface / processing system 82, whereas in the embodiment of Figure 1A, a wired connection 90 is used. The proximal connector and transmitter also include a power source, such as a battery, in one embodiment. Both of these proximal connectors include an electrical or optical connection to a sensor array located at the tip of the probe. The proximal connector may also include interface circuitry that forms a wired or wireless bridge to a measurement system, such as the probe interface / processing system.

[0071] In a wired connector system using an electrical pressure sensor, the interface electronics, as shown in FIG. 4A for example, are integrated into the display system 87 or another measurement system in one embodiment. The display system, interface / processing system, and other systems having inputs for receiving intravascular probe signals may be separate systems or may be combined at various levels as one or more systems, such as an ICD. Analog-to-digital conversion, signal processing and conversion of raw signal data to calibrated data, and graphical user interfaces for real-time presentation of pressure, flow, and temperature data may be implemented in one or more of the systems described herein that directly or indirectly receive the probe signal or data including data generated from the probe signal or data received from a given intravascular probe.

[0072] These interfaces or interface devices are connected to one or more circuits or signal processing or control elements. These circuits, elements, and other components of a given intravascular measurement system are used to convert the time-varying electrical signals from the guidewire-based probe into flow and pressure data. The time-varying electrical signals may be current, voltage, resistance changes, temperature changes, or other data that correlate with intravascular flow or pressure. These interfaces and displays are formatted and programmed to display one or more panels. The panels may include multiple display sections, such as those used by the measurement system for pressure data, ultrasound images, angiography images, OCT images, and other intravascular images and data. One or more such panels, such as D1, D2, and D3, may be controlled and programmed using the display system or other measurement system to display the flow data as a real-time curve in the time domain. Pressure data may be displayed simultaneously with the flow data. FFR values ​​based on the pressure data may also be displayed. Various trajectories and loops described herein may also be displayed along with points of interest.

[0073] The display system includes various panels, displays, or GUIs, such as D1, D2, and D3. These panels may present suitable intravascular measurement data, such as imaging data or pressure data or other data, such as angiography data, ultrasound data, or OCT data. For example, D1, D2, or D3 may display pressure vs. flow curves and real-time FFR data obtained using pressure measurements instead of other measurements. D1, D2, or D3 may also display other intravascular data of interest, such as imaging data, relative extrema, maximum flow, minimum flow, maximum pressure, minimum pressure, myocardial resistance, flow data, stent placement images, or other details of interest.

[0074] In one embodiment, the flow data is displayed in the same manner as the pressure data or in a coexistent or synchronized manner with the pressure data. For example, additional panels such as D1 or D2 or D3 may be added to an existing user interface or data display screen of a measurement system such as an FFR system or a combined or multimodal intravascular data acquisition system. These two or more additional panels may display pressure and flow information simultaneously, for example, as a pressure vs. flow curve or other representation integrated with the FFR results. These displays or interfaces may be part of an interface device of a guidewire-based probe, OCT, FFR, IVUS, or other intravascular data acquisition system, or may be in electrical communication, such as wireless communication, with the interface device. In one embodiment, a transfer or calibration function is used to calibrate the guidewire-based probe, and these functions use parameters stored in memory as inputs as part of a calibration system 93. The calibration system 93 may be part of a control system 92 in one embodiment.

[0075] D1, D2, and D3 may provide a user interface for operation of the flow and pressure measurement system. Additionally, information or graphical user interface panels D1, D2, D3, etc. may be used to display one or more of the plots or parameters depicted in Figures 7A-10B. Illustrated are D1, D2, and D3 by way of example and not limitation. Thus, various additional or subtracted displays, panels, or sub-panels may be used for one or more types of real-time data, stored data, and user interfaces described herein.

[0076] In a wireless probe-based system, in one embodiment, the interface electronics are contained in the proximal connector and transmitter. In one embodiment, analog-to-digital conversion of signal data acquired of blood flowing through a vessel is performed in the proximal connector. Further conversion of raw data to calibrated data may be performed by circuit elements or a processor in the proximal connector and transmitter or in the display system. A graphical user interface (GUI) for real-time presentation of pressure, flow, and temperature data may be implemented in the display system in one embodiment.

[0077] The embodiments of the present disclosure relate, in part, to various features of pressure sensing devices, measurement systems, and associated software suitable for pressure and flow monitoring. Pressure and flow monitoring may be performed using a guidewire-based probe having semiconductor elements including components that generate electrical changes in response to flow and pressure changes. For some clinical measurements, e.g., coronary flow reserve (CFR), coronary flow rate reserve (CFVR), fractional flow reserve (FFR), and myocardial resistance index (IMR), it is desirable to perform pressure and flow measurements simultaneously. In one embodiment, a maximum flow value or other flow value of interest (e.g., in an area of ​​a PQ plot) is identified using any of the embodiments described herein such that one or more of the CFR, CFVR, FFR, or IMR can be performed in response to such value. The embodiments described herein support methods of performing the above procedures and measurements using a guidewire-based probe and associated software and electrical components of a measurement system.

[0078] Using a guidewire-based probe in combination with the measurement platform and software methods described herein, pressure and flow can be measured simultaneously based on changes in the electrical signal. These components provide diagnostic tools and various interface types that aid in displaying the data in real time. Given that such data can be obtained from the electrical signal from the guidewire-based probe, pressure and flow data can be displayed while the probe is in the patient. The pressure and flow data can then be plotted together in real time as a pressure vs. flow, or PQ plot, and used to trigger events or as diagnostic tools as described herein. Stents can be deployed along the guidewire of the probe or using other catheter deployable wires or devices at locations identified by an angiography system or other imaging system co-registered with the location of the pressure and flow probe in the patient and its output data.

[0079] As shown in FIG. 2A, a blood vessel 100 is illustrated, which may be, for example, a portion of a coronary artery. Blood flows through the blood vessel 100 and throughout the rest of the artery, and when the blood encounters a constriction in the flow path, such as the constriction 120 shown, a change in flow rate and a drop in pressure occurs. The wall 150 of the blood vessel 100 surrounds a lumen 200 through which the blood flows. To obtain data about the blood vessel 100, a pressure sensor-based device 250, for example a guidewire-based probe, may be inserted into the lumen 200 of the blood vessel 100. A sensing region 300 of the device 250, where flow and pressure sensing occurs, is exposed to the blood, but may be surrounded by a capsule, jacket, or other structural support or other structure. The capsule, jacket, or other elongated support region or member provides structural support while allowing the sensing region to be open.

[0080] As shown in FIG. 2A, a guidewire 320 including electrical leads in communication with circuit elements in region 300 can be used to introduce device 250 into the lumen 200 of the blood vessel. Guidewire 320 is part of a guidewire-based probe in one embodiment. Pressure sensor-based device 250 is typically placed in a catheter (not shown). Measurements can be taken in the catheter during which flow is inhibited or substantially zero to provide a baseline or calibration value for flow. The guidewire can extend into a wireless proximal connector PC in one embodiment.

[0081] In one embodiment, electrical leads located in the guidewire and guidewire-based probe may extend into a connector or wireless device and data may be relayed to a probe interface system 340, also referred to as an interface device. The probe interface system or device 340 may perform calculations of measurements based on signals from the probe. Alternatively, the system 340 may receive signals that encode the results of calculations performed using circuitry or processing elements located in the probe (e.g., in the proximal connector of the probe). In one embodiment, the interface device 340 is a component or subsystem of a measurement device. In one embodiment, the interface device 340 is in communication with a measurement system 390, which may include a display device or an ICD. The systems 340 and 390 may include power supplies and other adapter components to provide and control over temperature or excitation voltages as described herein. The adapter components may be used to retrofit existing pressure monitoring systems.

[0082] The measurement or interface device 340 may include circuit elements selected to interface with or operate with those located within the guidewire-based probe. The interface device may also include software, a control system, and a data analysis / display device and processor suitable for graphically displaying pressure, flow, and their associated relative extremes. In one embodiment, the control system is programmed to trigger a pressure measurement, flow measurement, or otherwise perform an FFR, CFR, CFVR, or other procedure or calculation, when any of the following occur: maximum flow, maximum pressure, relative maximum flow, relative maximum pressure, and other values ​​or thresholds.

[0083] FIG. 2B shows further details regarding the sensing region 300 of the guidewire-based probe of FIG. 2A. The guidewire 320 typically includes the sensing region 300, which may be covered or otherwise supported by a capsule that is partially exposed to the blood flow. The sensing region may be cooled directly or indirectly by the blood flow. The temperature of the sensing region may be raised to a temperature comparable to or higher than the blood flow. Without being limited to a particular mechanism, in one embodiment, the blood flow contacts the sensing region 300 and induces heat transfer from the sensing region 300. In another embodiment, the blood flow induces heat transfer from the capsule and other materials of the guidewire or other support structure that are disposed around and in thermal communication with the sensing region 300. Thus, the sensing region, capsule, and surrounding materials may be sized and made of suitable thermally conductive materials to increase the amount of heat transfer and thereby improve the detection of blood flow parameters.

[0084] In one embodiment, as shown in FIG. 2B, the sensing region 300 of the guidewire-based probe is in fluid communication with the surrounding blood. The sensing region is bounded by a capsule or other barrier disposed around the sensing region. In one embodiment, the sensing region is cooled directly by the blood flow. In another embodiment, the amount of heat transfer through the capsule or other probe components supporting the sensing region is correlated with one or more blood flow parameters. Efficient heat transfer to the sensing region, whether or not it is in direct contact with the surrounding blood, increases the thermal response and accuracy of the flow measurement. In one embodiment, there is no capsule.

[0085] In one embodiment, a piezoelectric membrane 350 is disposed on a semiconductor substrate 400. The membrane 350 moves in response to pressure changes and provides an active resistance R A On the other hand, a passive resistor R P A reference resistor, also referred to as a pressure sensor, is also disposed or formed in the pressure sensor. The pressure sensor and reference (passive) resistor may be electrically connected to one or more electrical leads or other electrical components in various configurations for various embodiments of the probe.

[0086] For example, the electrical conductors L1 and L2 shown in the figure each have a resistance R P and R A In an alternative embodiment, FIG. 2C shows a semiconductor chip portion 128 of a guidewire-based probe device, which includes a semiconductor substrate and an active resistor R A and passive resistance R P In one embodiment, one or more electrical leads, such as leads L1 and L2, are connected to the measurement system 340 through a coupler or terminal end of a guidewire that is incorporated as part of the guidewire-based probe. A ground connection may also be a separate connection from the guidewire-based probe, as shown in FIG. 2B. A pressure sensor may also be implemented using an optical sensor, such as a fiber optic etalon. This optical sensor may be integrated with other hot wire anemometry devices. Temperature, pressure and flow data collection

[0087] A pressure sensor based device includes a miniature pressure sensor mounted on the tip of a guidewire as described herein. The pressure sensor is typically disposed on or formed from a semiconductor substrate, as shown in Figures 2B and 2C. As shown in Figures 1A and 1B, the pressure sensor is part of a sensor array that interfaces with the guidewire and is supported in part by a capsule. In one embodiment, the sensor array includes one sensor suitable for performing flow measurements, pressure measurements, or both. Figure 2D shows an exemplary representation of an intravascular probe 220 having a sensing device, e.g., capsule 50, and sensor array 43. The guidewire based probe 220 includes two or more measurement resistors, e.g., R, as part of the sensor array. A and R P The pressure sensor may include R in FIG. A The sensor has a membrane with a tensile resistance in communication with the membrane indicated by R. When the pressure changes, this affects the sensor membrane and creates an active resistance R A The resistance value of the tensile resistance, also called the resistance of the load, changes.

[0088] R A is typically temperature sensitive. A similar reference resistor, i.e., a passive resistor R P is placed on the substrate 400 and is sensitive only to temperature. This reference resistor facilitates compensation for temperature changes that may alter the pressure signal or act as noise. As a result, in one embodiment, one resistor in the guidewire-based probe is sensitive to both pressure and temperature (R A ), the other resistance of the guidewire probe is sensitive only to temperature (R P ).

[0089] These resistors are connected to measurement electronics, which may be located within the interface device or measurement system, or may be in electrical communication with the interface device or measurement system by a microcable. The cable selected is sized to fit the guidewire. Because the cable is thin, r a , rp , and r g has a fairly large resistance, typically about 40 ohms to about 70 ohms depending on the length. The microcable is also temperature sensitive. An electrical equivalent model is shown in FIG. 3. The sensor array is connected to an elongated guidewire, shown diagrammatically, which extends to a proximal connector. As shown in FIGS. 1A and 1B, the proximal connector may include a transmitter in a wireless embodiment, or in an alternative embodiment, a wired connection may be used for data signal transmission. Guidewire-Based Probe Capsule and Flow Directing Components

[0090] FIG. 2D shows the tip 220 of a guidewire-based probe with the sensor array 43 as shown in FIGS. 1A, 1B, 2A, 2B, and 2C exposed through an opening in the capsule 50. The capsule or jacket may be a tube with an opening in the side that abuts against the guidewire portion as shown to define an opening through which one or more components of the sensor array are visible. The role of the capsule is to provide structural support for the guidewire-based probe while allowing blood flow through the sensing region and to remain in contact with and cool the tip of the probe. In one embodiment, the capsule can be thinned or eliminated to reduce the V TOFFS -V P The signal sensitivity is increased. It is therefore possible to use integrated pressure and flow measurement probes, with or without a capsule. Electrical Interface Components

[0091] R A and R PWhen a guidewire-based probe including a pressure and flow meter is used to measure pressure and flow, the probe transmits data to an interface or display system. Such systems are, for example, the RadiAnalyzer, RadiAnalyzer Xpress, Quantien, or Aeris systems. In one embodiment, the arrangement of the guidewire-based probe device and its circuit elements is shown in FIG. 3, which forms a bridge. This is, for example, a Wheatstone bridge when connected with the electronic circuitry of the measurement system, as shown in FIG. 4A.

[0092] As shown in the circuit diagram in Figure 3, R A and R P represents the resistance on the semiconductor substrate 40, and r a , r g , and r p corresponds to the microcable including the bonds and connectors of a given guidewire-based probe. The resistance of the cable to ground is r g The active resistance R A and passive resistance R P may range from about 2200 ohms to about 3200 ohms, and may typically be 2700 ohms. A The pressure sensitivity of the sensor is at least about 7.9 ppm / mmHg, and typically about 10 ppm / mmHg. Thus, for a typical guidewire-based probe sensor, the ratio of resistance to pressure sensitivity is about 2700×10 / 1000000=27 mΩ / mmHg. A and R P The temperature sensitivity of is at least 400 ppm / °C, typically 500 ppm / °C. That is, for a typical sensor, the ratio of resistance to temperature is about 2700 x 500 / 1000000 = about 1.35 Ω / °C. A change of 0.02°C reduces the active resistance R A This corresponds to a change of 1 mmHg.

[0093] FIG. 4A shows the electronics of the interface or measurement system that interfaces with the electronics of the guidewire-based probe. aThe active resistor and active resistor connecting cable having the active resistor R1 and V2 interface with node A of the interface system or measurement system. Node A is then in electronic communication with resistor R1 when the guide wire-based probe is connected to a measurement device. In one embodiment, a signal is applied from node A to V1. A is measured. The resistance value r p A passive resistor and passive resistor connection having V interfaces with a node P of the interface system or measurement system. And, node P is in electronic communication with resistor R2 when the guidewire-based probe is connected to a measurement device. In one embodiment, a passive resistor and passive resistor connection having V P is measured.

[0094] Resistance value r g A ground cable having an excitation voltage V is connected to ground G. EXC is applied to resistors R1 and R2. R1 and R2 are located in one or more systems, such as a probe interface system. In one embodiment, V EXC is the excitation voltage of the Wheatstone bridge. In one embodiment, the bridge excitation voltage ranges from about 1 volt to about 15 volts. R1 and R2, in one embodiment, may range from about 2000 ohms to about 3000 ohms. In one embodiment, the Wheatstone bridge is driven by an excitation voltage V EXC It is excited by the interface of a guidewire-based probe that uses V A Gato V P The potential difference between the V and V is measured to derive the pressure. TOFFS and V P It is measured between P OFFS The 10% constraint is chosen so that the voltage V TOFFS is approximately V at 37°C P This corresponds to an offset voltage approximately equal to

[0095] With further reference to FIG. 4A, a positive voltage V POFFS + and negative voltage V POFFS -Applied voltage as V POFFSV corresponds to the offset voltage used to level or balance nodes A and P on the Wheatstone bridge. POFFS is R A and R P V is the offset voltage used to balance the pressure channels to compensate for the resistance difference between POFFS is the temperature at about 37°C, and V is the temperature at zero pressure at standard atmospheric pressure (760mmHg). A and V P The potential between the electrodes is adjusted to zero.

[0096] As shown in FIG. 4A, the electrical components of the guidewire probe and the electrical components of the measurement system are connected to allow the excitation voltage applied in a bridge configuration or with respect to other current or voltage levels to be maintained as necessary to support the CTA or CVEX methodology. FIG. 5A shows how the voltage of the measurement bridge of FIG. 4A is sampled, converted, and processed in the DSP. V A and V P may be amplified with a programmable gain before analog-to-digital conversion.

[0097] The wireless interface system shown in Figure 1B has an electrical signal interface to the guidewire-based probe and the RadiAnalyzer, Xpress, Quantien, or ComboMap® Pressure and Flow System when connected thereto, which forms a measurement bridge with the wireless intravascular probe's transmitter, or an equivalent or similar interface. The guidewire-based probe interface device or measurement system includes interface electronics that sample the analog signal of a bridge, such as a Wheatstone bridge, or other balanced circuit configuration. An example of such interface electronics is shown in Figure 4B.

[0098] Specifically, FIG. 4B is a circuit diagram depicting interface electronics suitable for use with a wireless intravascular flow and pressure sensor. The area enclosed by the dotted line corresponds to the electrical components in an intravascular probe. For example, the embodiment of FIG. 1B is compatible with the interface circuit of FIG. 4B. The right side of FIG. 4B shows how the electronic components of a guidewire-based probe are connected to a constant current interface circuit. Constant current sources may be switched into contact with the circuit by switches S1, S2, S3, and S4. These switches may be physical switches, multiplexers, or may be implemented as software control of the current sources. Resistors R1 and R2 are precision fixed resistors. In one embodiment, one or more current sources I are located in the proximal connector. A voltage V TOFFS In one embodiment, V P The voltage difference V A -V P By measuring the temperature, a measurement of pressure can be derived. TOFFS -V P The constant current circuit causes current-induced heating of the tip of the guidewire-based probe sufficient to measure flow by flow velocimetry methods such as CVEX, CTA, etc. Switching the current source allows the acquisition of pressure and temperature values ​​(flow values) which can then be wirelessly transmitted to the measurement system. Modification of the conventional system embodiment

[0099] In one embodiment, the present disclosure relates to a system adapter for adapting or otherwise retrofitting into a measurement system such as a pressure measurement interface device (e.g., a device originally designed only for pressure monitoring). Thus, with the addition of the adapter, the sensing device is able to support simultaneous pressure and flow sensing with a guidewire-based probe. The adapter includes a power source having an output power range. In one embodiment, the output power range is greater than about 5 volts. In one embodiment, the output power range is greater than about 10 volts. In one embodiment, the output power range is about 12 volts or greater. In one embodiment, the adapter is a circuit board sized to be installed within the measurement system.

[0100] In conventional systems for collecting pressure, FFR, and other intravascular data, one or more circuit elements in the interface device of the guidewire-based probe may be modified or replaced to achieve a higher excitation voltage for the guidewire-based probe. In one embodiment, power supply components may be added or modified so that the excitation voltage applied to the sensing region is greater than about 10 volts. In another embodiment, a filter may be incorporated having a passband set to remove noise that extends down to the level of the flow parameter measurement signal.

[0101] Each pressure sensor based device has a memory storage device, such as an EEPROM. In one embodiment, one or more parameters obtained for the guide wire based probe (e.g., during manufacture of the guide wire based probe) are stored in the memory device. In one embodiment, the memory device is attached to the guide wire based probe. The memory device may be an EEPROM, RFID, or other suitable memory storage device. Storing one or more sensor parameters in a memory device associated with the pressure probe allows the parameters to be retrieved as needed. The parameters may be retrieved by a suitable scanner or interface device or component thereof and then used to calibrate the guide wire based probe prior to using the guide wire based probe to collect pressure and flow information.

[0102] In one embodiment, parameters stored in the probe include zero level or baseline temperature, zero level or baseline excitation voltage, and sensitivity coefficients associated with excess temperature. A pressure vs. flow curve may also be output. This is a curve showing the change in pressure and flow over time and with respect to location within the vessel. The stored memory parameters may be used to scale or calibrate the pressure vs. flow curve. Pressure and flow data may be displayed along with image data such as optical coherence tomography, ultrasound, angiography, etc.

[0103] In one embodiment, a memory containing individual unique calibration parameters set at the time of manufacture is placed at the connector end. These stored parameters are used by the guidewire-based probe interface device software to convert the sampled "raw" voltage into an accurate pressure value in mmHg. Specifically, the pressure sensor is calibrated at a final measurement station during the manufacturing process. The purpose is to ensure that the R A Pressure sensitivity, R A and R P Temperature Sensitivity of Bridge and V POFFS and V TOFFS The objective of the present invention is to measure the balance between the temperature and the temperature, the sensor current, and the temperature range. In one embodiment, the appropriate parameters are stored in a memory such as an RFID chip or an EEPROM, or other memory. In one embodiment, the memory is located in the connector of the guide wire-based probe. Flow measurement

[0104] When using a pressure sensor based hot film anemometer, the sensor array, e.g., the semiconductor sensor described herein, is heated by an electric current and the cooling effect of the blood flow is measured by a resistance R P It is measured by sampling the voltage across R P The voltage across R can be measured. PA circuit showing a suitable configuration of, as well as other resistors and electrical connections, is shown in Figure 4 A. This voltage may be used in two related flow velocimetry methods: CTA and CVEX flow velocimetry.

[0105] One consideration with pressure sensor based hot film anemometry is to realize that the electrical signal generated by the associated resistor does not distinguish between flow rate changes and blood temperature changes. If any unusual blood temperature changes occur, the system will interpret these as flow rate changes. Therefore, a feedback loop monitoring the subject's environment as well as patient temperature readings may be obtained using other temperature sensors. Notwithstanding the above, typically blood temperature may be considered constant given the duration of the procedure and the time it takes for blood temperature to change. Constant temperature flow measurement (CTA)

[0106] As an example, the guidewire-based probes shown in Figures 1A, 1B, 2A, and 2C and components described herein can be used as flow measurement devices and flow meters in a constant temperature mode, also referred to as constant temperature anemometry (CTA). A temperature sensitive resistor in the sensor tip of the guidewire-based probe is heated to a specific temperature above the ambient temperature by application of a controlled excitation voltage. The resistor is exposed to the surrounding fluid or is otherwise in communication with other thermally conductive materials that react to changes in blood flow, causing cooling and associated cooling changes in the sensor. Fluid flow, in turn, has a variable cooling effect on the resistor. An increase in flow rate increases the cooling effect, and a decrease in flow rate decreases the cooling effect. The temperature sensitivity (R P The excitation voltage is controlled by a digital system to a predetermined level so that the flow rate (V) is stable. The excitation voltage is therefore a measure of the flow rate.

[0107] Resistance of the pressure sensor R PThe temperature of the bridge is maintained at a constant level, typically in the range of about 10° C. to about 20° C. above the blood temperature. This constant temperature is controlled by the bridge excitation voltage. Higher blood flow results in more cooling and a higher bridge excitation voltage. Conversely, lower flow results in a lower excitation voltage. Thus, the excitation voltage is a measure of the flow rate. The guidewire-based probe interface device software controls the voltage V TOFFS -V P From R P The temperature is extracted and used as an input for the excitation voltage control system, which is also implemented in the guidewire-based probe interface device software as a proportional (P) controller as shown in Figure 5B. An embodiment of a CTA control system

[0108] FIG. 5A illustrates the principle of measuring flow rate using the constant temperature anemometry (CTA) technique with the measurement device of FIGS. 1 to 4. As shown in FIG. 5A, the difference V TOFFS -V P R is calculated by measuring and dividing this signal by the applied excitation voltage (VEX). P The temperature change of the microcable resistance r in Fig. 4 a , r p , and r g A signal that depends only on R is obtained. This temperature dependent signal is also called the Temp signal in FIG. 5B and is used as an input for the VEX control in the DSP software. The control system is designed to maintain a constant temperature signal by controlling VEX. The constant temperature signal is expressed as R P is the same as the constant temperature of the surface exposed to the fluid flow (in this case R P The basic idea behind CTA is to induce and maintain a certain excess temperature in the

[0109] For pressure measurements, as shown in Figure 5A, V A and V P The voltage difference between V ASince it is temperature sensitive and pressure sensitive, more than one signal is used to measure the voltage difference V A -V P In one embodiment, the voltage difference V A -V P is determined by using a control system or a control circuit or a signal processor to determine the voltage difference V A -V P Voltage difference V TOFFS -V P The temperature is compensated by processing with V TOFFS -V P is a signal that depends on temperature.

[0110] As shown in FIG. 5A, there are two signal channels: a pressure branch (V A and V P ) 505, and the temperature branch (V TOFFS and V P ) 507 is measured. The pressure branch is V A and V P The pressure signal is amplified by a programmable gain 510. Gain values ​​may be individually selected for each sensor in the guidewire-based probe and stored in the memory of a given pressure probe, or may be generated from information stored in that memory. In one embodiment, the programmable gain values ​​are calibrated such that 1 analog-to-digital conversion unit (ADU) corresponds to approximately 0.1 mmHg. An analog-to-digital converter (ADC) 520 converts the pressure value V A -V P The DSP 530 samples in response to the amplified value of , and outputs a pressure value in ADU. The gain value is read by the signal processing software of the DSP 530, which also loads the gain value into the gain circuitry of a digital-to-analog converter (DAC) as shown in FIG. 5A.

[0111] FIG. 5C shows a control system 580 for an intravascular measurement system based on the operating principle of CTA. P The control system is programmed to keep the temperature constant by controlling the signal V TOFFS -VP by VEX and use this signal, labeled "Measured Temperature" in Figure 5C, as an input to the control system to obtain R P The control system measures the temperature change at a specific R P The set point temperature and the measured R P The difference between the temperature of and is the system error, multiplied by a coefficient k. The result of this multiplication is added to the excitation voltage from the previous control iteration to generate a new excitation voltage, which is used to adjust the sensing circuitry at the tip of the probe.

[0112] Before the control system is initiated, a set point value based on the temperature of the fluid is established. The set point is determined by converting the measured temperature signal at VEX in the range of about 0.5V to about 2V to a Celsius value using ADU-to-Celsius conversion parameters stored in the guidewire-based probe's memory. A user-defined excess temperature is added to this measured temperature of the fluid to determine the set point in Celsius. The temperature representation of the set point is then converted to an ADU (Analog Digital Unit) value and used as the set point for the control system. The ADU-to-Celsius conversion parameters stored in the intravascular probe's memory storage or another memory location are used to convert to an ADU set point. In one embodiment, the user can set the excess temperature using the measurement system interface.

[0113] As shown in FIGURE 5C, a summer Σ 585 adds the inverted (-1) measured temperature 595 to the set point temperature 582 to generate an error 587 for the active control system. This error is multiplied by a factor k and then added 591 to the previous excitation voltage, as shown in processing step or stage 590. This scaled error is used to generate a new excitation voltage level. This new excitation voltage may be applied to an intravascular pressure and flow monitoring probe 592, which in turn allows for sampling of intravascular data and generation of a measured temperature 594.

[0114] The measured temperature shown in Figure 5C is TOFFS -V P This division by the excitation voltage results in a signal that depends only on the temperature change. The set point temperature is stored in the pressure sensor's memory. For example, if the memory set point parameter is 10, the system software or control system will set R P The temperature of the blood is kept 10° C. above the blood temperature. For an excess temperature of 10° C., the excitation voltage ranges from about 5 volts to about 7 volts. For higher excess temperatures (greater than 10° C.), in one embodiment, it may be necessary to use a higher voltage range, i.e., greater than 7 volts. These excitation voltage changes track changes in flow rate. Constant Excitation Voltage

[0115] In one embodiment, flow and pressure measurements are made using a fixed excitation voltage (e.g., about 5 volts). In one embodiment, the CVEX approach does not include a control system algorithm. It uses the voltage V TOFFS -V P Instead, for the control system of FIG. 5C, a flow value calculation algorithm is used instead of controlling the change in VEX as described above. In contrast, R P The temperature of R changes with the flow rate. P Conversely, if the flow rate decreases, the temperature of R P 5D shows a flow measurement system 600 processing signals from a guidewire-based probe while using a constant excitation voltage, i.e., CVEX.

[0116] As shown in FIG. 5D, the DSP software embodiment of the present disclosure converts the Temp signal (sampled V TOFFS -V PThe VEX receives a Temp signal. VEX is constant and is set by the DSP software and converted to an analog signal by a Digital to Analog Converter (DAC) 620. The Flow Calculation Algorithm 615 receives the Temp signal as an input and is capable of generating a Flow value from this signal.

[0117] 5E is a schematic diagram of a software embodiment of a simultaneous pressure and flow measurement system 650 using the CVEX method. As shown, the probe interface / measurement system software 660 receives an input voltage difference from an analog-to-digital converter 665. The difference signal V A -V P and the difference signal V TOFFS -V P is processed to generate a pressure value that can be displayed as a value or plot on a console or other display as described herein. Meanwhile, the difference signal V TOFFS -V P are processed to generate flow values ​​or plots on a console or other display as described herein. These values ​​may be displayed, plotted as a pressure vs. flow curve, and in another form may be used as input for FFR calculations by the measurement system or calculated by circuitry or a processor built into the probe itself. Characteristics and implementation of CVEX and CTA transfer functions

[0118] The applied excitation voltage (when using a CTA) or the measured temperature (when using a CVEX) can be converted to a flow rate value or converted to a value that correlates to the flow rate by a transfer function. In one embodiment, the transfer function is determined by exposing the pressure sensor to a known reference flow rate and plotting the measurement signal against the reference flow rate. The reference flow rate can be generated using a fluid flowing in a closed loop system, for example, water flowing in a loop tank or curved tank. Figures 6A and 6B show a typical relationship between the measurement signal and the reference flow rate.

[0119] 6A and 6B show curve fitting performed to determine an appropriate transfer function relating flow rate x to temperature or excitation voltage T(x) for both CTA and CVEX, respectively. A pressure sensor based device can be calibrated by exposing the device to several flow rate levels and then curve fitting or otherwise determining the constants a and b of the respective function T(x)=a+b×lnX. In the case of CTA, the output of T(x) is the excitation voltage and in the case of CVEX, the output of T(x) is the temperature. The constants (a and b) of this transfer function may be stored in the memory of the pressure sensor.

[0120] Additionally, the inverse of the function a+b×lnX is used by the guidewire-based probe interface device software to calculate flow values ​​as part of a flow calculation algorithm. By tracking flow values ​​over time, points of maximum flow may be displayed. Using points of maximum flow or relative extrema generated using a pressure versus flow plot or other representation, it is possible to identify multiple time points or locations along the vessel between which images may be overlaid or measurements (e.g., a series of FFR measurements) may be taken corresponding to multiple time points and flow levels spanning one or more of the maxima, minima, or relative extrema.

[0121] There are some differences between the CTA and CVEX methods that should be considered. Figures 6A and 6B show that CTA and CVEX have the same type of relationship between units of flow and units of the measured quantity (a+b x lnX). Furthermore, both methods have comparable accuracy (as observed in laboratory tests) in measuring pulsatile flow. Therefore, the CVEX and CTA methods may be considered comparable when it comes to measuring flow. In one embodiment, the CVEX approach may be advantageous when measuring flow and pressure simultaneously, as it simplifies the pressure measurement. In the CTA approach, the pressure measurement is more complicated due to the varying excitation voltage. In one embodiment, the hardware and software of the CTA pressure and flow measurement system are selected to accurately measure pressure while controlling the excitation voltage to within narrow error limits. Adapting FFR and other measurement platforms to measure pressure and flow

[0122] A system for simultaneously measuring pressure and flow rate may typically be implemented based on the CVEX principle. Implementing CVEX flow rate measurement in a pressure sensor measurement system is possible by using a circuit board or adapters such as circuit and power supply, and by modifying the software and control flow.

[0123] From a device or hardware standpoint, it is useful to increase the maximum excitation voltage output to the Wheatstone bridge of the pressure sensor measurement. As part of the process of retrofitting an intravascular measurement system (e.g., a system that measures pressure only) for simultaneous pressure and flow monitoring, a power supply unit (PSU) board with a 12V output may be installed on the guidewire-based probe interface device board. Additionally, one or more amplifiers in the guidewire-based probe interface device are biased at +12V and -12V instead of the usual ±5V used for pressure sensing.

[0124] In one embodiment, the interface software of the guidewire-based probe controls the voltage VTOFFS -V P is sampled at a sampling rate approximately in the range of about 400 Hz to about 600 Hz. This sampled signal is stored in memory. In one embodiment, this signal is stored as a variable typically denoted TEMP in a specific location in a signal data array. This CVEX implementation converts the voltage difference stored as the TEMP signal into a flow value using a transfer function described herein. A software representation of this signal processing is shown in FIG. 5E. These hardware and software features provide a system where the CVEX approach can simultaneously measure pressure and flow using a pressure sensor.

[0125] The flow measurement systems described herein may be implemented with certain temperature related design modifications, including implementing one or more of cable temperature compensation and flow insensitive absolute temperature measurement. Embodiments of a Cable Temperature Compensation Method

[0126] Switches S1 and S2 of the measurement bridge of the guidewire-based probe of FIG. 4A (which are typically "on" during normal operation of the guidewire-based probe interface device) allow either branch of the bridge to be switched off. When S2 is switched off, the resistance changes (i.e., temperature changes) of the microcables ra, rp, and rg are converted into voltages (V TOFFS -V P ) during both states of S2. TOFFS -V P By sampling, the temperature signal of the sensor array may be extracted as follows: Sensor temperature = (S2_on_V TOFFS -V P )-k×(S2_off_V TOFFS -V P ) However, (S2_ON_V TOFFS -V P ) is the signal sampled while the S2 switching element is in the “on” state, and (S2_off_V TOFFS -V P ) is the signal sampled while the S2 switching element is in the "off" state, and k is a compensation constant associated with the particular probe interface device. The value of k may be stored in memory and accessible as needed by the sensor temperature determination method.

[0127] This cable temperature compensation method determines the sensor temperature and eliminates or reduces the effect of cable temperature changes on the flow signal. Specifically, the method of compensating for cable effects using a "switch on" signal with a "switch off" signal produces a signal that is responsive only to sensor temperature changes associated with the sensor array in the intravascular probe tip. This is desirable because normal handling and clinical use of guidewire-based probes causes temperature changes in the microcable.

[0128] These induced temperature changes can cause degradation of the uncompensated (switching element S2 in the "on" state) signal as a result of changes in the cable resistance. TOFFS -V P Because a signal is used, the cable temperature compensation method described herein produces a signal that is responsive only to temperature changes at the probe tip sensor. Furthermore, when blood temperature is stable, as typically occurs when a patient is resting in a constant temperature environment, only temperature changes relative to the sensor will correspond to changes in the flow parameter. In one embodiment, the flow parameter is flow velocity. In another embodiment, the flow parameter is flow rate. Flow-insensitive absolute temperature measurement embodiment

[0129] Using the cable temperature compensation described herein and reducing the excitation voltage to about 0.5V results in a system that measures blood temperature changes (or temperature changes of whatever medium the probe is inserted into). The excitation voltage is advantageously selected to be in the range of about greater than 0 volts to about 2 volts, as this will result in the temperature of the sensor array being approximately the same as the temperature of the surrounding blood. As a result, by selecting the excitation voltage such that the temperature of the sensor and the fluid are approximately matched, the pressure and flow monitoring system will be insensitive to changes in flow rate. This is because the flow measurement is based on generating a sensor array temperature in response to the excitation voltage, which may be affected by cooling from the surrounding fluid as it flows relative to the probe tip. This allows the blood flow rate to be measured, as opposed to simply measuring changes in blood temperature.

[0130] The sensor temperature signal defined above is, in one embodiment, measured at an excitation voltage of 0.5 V. The absolute temperature of the fluid (blood) may then be calculated using the difference relationship between the first constant and the product of the second constant and the sensor temperature as follows: Absolute temperature = CD (sensor temperature) where C and D are constants specific to the particular interface or processing system, or associated integrated system, receiving data from a given intravascular probe and its sensor array. The sensor temperature referred to in the absolute formula above is the temperature when the sensor temperature is (S2_on_V TOFFS -V P )-k×(S2_off_V TOFFS -V P ) the constants C and D are specific to each combination of intravascular probe and each interface or processing system. These constants C and D may be encoded in a memory attached to each probe in one embodiment.

[0131] Cable compensation and absolute temperature measurements are useful features in a flow measurement system, in part because signal effects from the resistance of the microcable are eliminated. Additionally, it is useful to monitor blood temperature during flow measurements, since the flow measurement signal is sensitive to both changes in flow rate and blood temperature. User operation of the measurement system allows the user to manually switch between flow and absolute temperature modes. FFR measurement and its applications

[0132] In one embodiment, one or more pressure vs. flow plots are obtained after administration of a hyperemic agent. In one embodiment, one or more pressure vs. flow plots are obtained without administration of a hyperemic agent. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular related measurements are obtained after administration of a hyperemic agent. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular related measurements are obtained without administration of a hyperemic agent. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular related measurements are obtained during periods of high or peak flow identified by measurements from pressure and flow sensors within the vessel.

[0133] In one embodiment, the FFR value or related value is obtained based on the ratio of distal to proximal pressure of the vessel (Pdistal / Pproximal). In one embodiment, the FFR value or related value is obtained based on the ratio of occluded peak flow to non-occluded peak flow. These various techniques for obtaining flow data (e.g., flow velocities at multiple locations within the cardiovascular system) may be displayed individually or together with other cardiovascular values, as ratios, or through other relationships indicative of the subject's condition.

[0134] In one embodiment, an intravascular probe is moved along the length of the artery and a data set of one or more pressure measurements, flow parameter measurements, and position measurements are acquired over time. Elements of this data set may be synchronized and registered with each other with data from IVUS, angiography, OCT, or other additional sensors. This data set can be processed to calculate measurements of distal pressures, such as distal coronary pressure, and proximal pressures, such as aortic pressure. From these distal and proximal pressures, multiple FFRs can be calculated using the following relationship: i You may get the value. FFR i =P 遠位I / P 近位I =maximum occlusion flow / maximum non-occlusion flow The i value may be selected as an index into the set of elements (eg, flow parameters, pressure values, etc., occluded / unoccluded maximum flow rates) obtained for the vessel.

[0135] FFR may be evaluated as the maximum blood flow in the presence of a stenosis (first flow) divided by the maximum blood flow in the absence of a stenosis (second flow). The ratio of these occluded and unoccluded maximum flows provides the FFR value in terms of flow ratio. These flows can be obtained using the intravascular probes described herein.

[0136] In one embodiment, FFR values ​​acquired during periods of maximum or minimum flow are evaluated to determine FFR values ​​based on events occurring during these respective measurement times and the locations on the vessel where they were acquired. In one embodiment, the minimum FFR value acquired, or the FFR value acquired for maximum flow or average maximum flow, is displayed as the FFR value. Pressure and flow plots and trajectories

[0137] In one embodiment, the disclosure relates to performing pattern recognition on pressure versus flow plots or data sets generated using CTA or CVEX methods. This pattern recognition may be performed using a processor in a measurement device or another device that receives data generated by an intravascular pressure and flow probe. This pressure versus flow plot can be displayed in real time or near real time as a response to the simultaneous collection of pressure and flow data by a guidewire-based probe. The pattern recognition process can compare pressure versus flow trajectories or patterns, or subsets of such curves, and correlate them with conditions or patient states of interest.

[0138] In one embodiment, patient data from a healthy population is used to establish a baseline signature, such as a trace or trajectory of a PQ plot, for comparison with individuals needing diagnostic information. Individual traces can also be obtained for individual patients and compared with subsequent traces to indicate the effectiveness of a given treatment plan or procedure. Assessment of the quality and duration of recovery can also be performed using pressure versus flow curves and other plots and FFR values ​​obtained before and during the procedures described herein (e.g., stent procedures).

[0139] A graphical user interface (GUI) of the measurement or display system displays the flow data as real-time curves in the time domain. Pressure and flow data can be plotted together in real time to generate a PQ plot, which is shown in FIG. 7A with further details regarding pressure and flow ranges. As noted in the legend for each plot or described herein, the following designations are used to identify each curve: G for green, B for blue, and R for red. G is generally used to indicate curves associated with the right side of the heart. R is generally used to indicate curves associated with the left side of the heart. B is generally used to indicate curves associated with blood pressure versus time.

[0140] In one embodiment, the pressure vs. flow curve includes relative extrema, inflection points, maxima, and minima that correlate with one or more dynamic events, cardiac cycle events, cardiac conditions, degree of stenosis, pre-stent flow, post-stent flow, degree of recovery after a cardiac event, comparison with historical data, and data obtained at various time points, which in one embodiment may correlate with the introduction of one or more drugs or treatment regimens (e.g., a stent).

[0141] In one embodiment, the pressure vs. flow curves may be used to calibrate pacemaker function. This may be done by obtaining the patient's pressure vs. flow curves and monitoring how they change over time and converge to one or more trajectories or shapes. In one embodiment, the pacemaker may be adjusted by using the historical and current pressure vs. flow plots to follow the trajectory of a healthy heart. In this manner, the pacemaker's operating parameters may be adjusted and calibrated. The pressure vs. flow curves may also be used to determine pressure and flow readings before and after renal denervation to provide efficacy and diagnostic information. In one embodiment, the guidewire-based probe may be placed at various locations in the artery (e.g., near the main artery or a branch) while collecting pressure and flow data. The location of the change in flow from one branch to another may be used to classify a given branch as potentially occluded. These locations may be identified by IVUS, OCT, angiography, and other imaging modalities during the procedure.

[0142] The following provides a detailed description of various exemplary curves that can be obtained using pressure and flow sensing probes. These curves are generated using sensor data acquired at one or more locations within an artery by an intravascular probe that includes sensors suitable for simultaneously measuring pressure, temperature, and flow. This sensor data can be used to generate one or more of the following values ​​and representations of information: signatures, trajectories, slopes, maxima, minima, ratios of measurements, ratios of measurements to derived values, ratios of first derived values ​​to second derived values, ranges, FFR values, CFR values, CFVR values, IFR values, IMR values, indices, patient status, and other values ​​and representations of information described herein.

[0143] The individual data elements and curves that evolve and change over time can be used for various diagnostic purposes as described herein. In one embodiment, the trajectory or shape or range (or other features) of the pressure vs. flow curve can be fitted to historical data, such as data such as the patient's age, weight, activity level, and one or more patient conditions (e.g., heart attacks, valvular damage, and other measurable patient parameters), allowing the pressure vs. flow curve of a new patient to be compared to pressure vs. flow curves representative of a particular patient condition to aid in diagnosis.

[0144] 7A shows a plot of time versus flow using a reference flow probe identified with an R or red or other first indicia and a guide wire based pressure and flow probe identified with a B or blue or other second indicia. Both the reference flow probe and the guide wire based pressure and flow probe embodiments were exposed to pulsatile flow in a water circulation loop. The reference flow pattern and the measured flow pattern reveal a linear relationship between the applied flow rate and the measured signal.

[0145] 7B shows a plot of the measured temperature (flow) signal rising in response to the guidewire probe being pulled back from the distal left anterior descending artery (dLAD) position to the proximal left anterior descending artery (pLAD) position. The pressure signal remains approximately constant as the guidewire probe is pulled back through the artery.

[0146] FIG. 8A shows plots of pressure and flow versus time obtained using pressure and flow sensing probes in a 40 kg pig. The proximal right coronary artery (pRCA) (right side) is where the sensing probe is monitored. Pressure and flow are shown on the vertical axis versus time on the horizontal axis. The small bumps at the bottom of the curves are small scale regurgitant flows. The dotted lines show pressure values ​​that generally rise and fall in a pattern that correlates with the flow shown in the lower curve. The phase of the pressure and flow curves are aligned for the pRCA data shown in FIG. 8A.

[0147] FIG. 8B shows a plot of pressure and flow versus time obtained using pressure and flow sensing probes on a 40 kg pig. The pLAD is where the sensing probe is monitored. Pressure and flow are shown on the vertical axis versus time on the horizontal axis. The small bumps at the bottom of the curves are small scale regurgitant flows. Unlike FIG. 8A, the pressure and flow curves are out of phase in FIG. 8B and the peak of the pressure signal appears to be shifted to the right relative to the flow signal. As shown in FIG. 8A and FIG. 8B, the flow peaks appear to be on the right during systole and to the left during diastole.

[0148] FIG. 8C shows a pressure vs. flow plot obtained using a pressure and flow sensing probe on a 40 kg pig. The proximal right coronary artery (pRCA) is where the sensing probe is monitored in FIG. 8C. The loop direction is clockwise. Various points of interest A, B, C, and D are shown. Any point may be selected as the starting point, but starting from point A on the bottom left, a trajectory or loop can be traced. In one embodiment, the shape or extent of the loop can be saved and compared to other loops to identify correlations. The shape or loop may be monitored for contraction, expansion, slippage, or other changes before, during, or after treatment.

[0149] For example, the path along the loop from point A, which corresponds to a state of low flow and low pressure, can follow the loop up to point B as pressure increases, then move to the right along a path that is nearly horizontal as flow increases, to point C. From point C, as pressure and flow decrease, follow an angled path to point D, then loop back to point A. Point A corresponds to the state of low flow and low pressure that characterizes the beginning of contraction. Point B corresponds to the state of maximum pressure and minimum flow that occurs during systole. Point C corresponds to the state of maximum pressure and maximum flow that occurs during systole. Point D corresponds to a transition state between A and C, with a relative extremum corresponding to the second-highest flow during diastole. This flow at point D is retrograde.

[0150] FIG. 8D shows a plot of pressure and flow versus time obtained using pressure and flow sensing probes on a 40 kg pig. The proximal RCA is where the sensing probe is monitored. Points A, B, C, and D in FIG. 8C are also shown in FIG. 8D. These points show the increase in pressure and flow as contraction begins, followed by a decrease in pressure and flow during diastole after the heart contracts.

[0151] FIG. 8E shows a pressure vs. flow plot obtained using a pressure and flow sensing probe on a 40 kg pig. FIG. 8F shows a pressure and flow plot against time corresponding to the data of FIG. 8E. The proximal left anterior descending coronary artery (pLAD) is where the sensing probe is monitored. The loop direction is clockwise. Various points of interest A, B, C, D, E, and F are shown. Most of the selected points of interest B, C, D, and E occur during systole, while points A and F occur during diastole. Point A corresponds to the maximum flow rate in diastole after the systolic signal contraction. Point B corresponds to the minimum pressure value that occurs at the beginning of contraction. Point C corresponds to a relative local increase in pressure before reaching the maximum pressure at point D. Point E corresponds to the aortic valve closing and the pressure in the left ventricle decreasing. Thus, as shown in FIG. 8E, the pressure decreases and blood flow in the left coronary artery increases again.

[0152] FIG. 9A shows pressure and flow versus time at the pLAD. FIG. 9B shows myocardial resistance versus time. The locations of maximum flow and minimum pressure are identified. The location of minimum myocardial resistance at maximum flow is identified. Myocardial resistance for minimum pressure is also identified and plotted. These resistance values ​​can be used to establish a trajectory of change over time and may be displayed to the user in real time or near real time along with FFR and other values ​​obtained using an intravascular pressure and flow probe that can simultaneously measure the above parameters. These measurements were taken on a 40 kg pig.

[0153] 10A and 10B show pressure and flow plots (top) along with a plot of time versus flow (bottom). FIG. 10A corresponds to a normal scenario, and FIG. 10B corresponds to an abnormal flow scenario due to an artificially induced partial occlusion of the marginal branch. The illustrated pressure (P) versus flow (Q) trajectory resembles a tilted figure eight, or an infinity symbol, as plotted in the upper left corner of the pressure versus flow plot in FIG. 10A. In the case of the normal scenario in FIG. 10A, the trajectory has approximately equal lobes. In contrast, in the corresponding plot in FIG. 10B, of the abnormal example after an artificial occlusion has been induced, the trajectory is asymmetric, with the left lobe contracting and the right lobe expanding. In one embodiment, these can be used as signatures to identify abnormal cardiac events. Similarly, the double-peaked flow versus time curve in FIG. 10A becomes a more rounded and larger amplitude curve in the abnormal scenario in FIG. 10B. In one embodiment, this amplitude shift, rounding, and double peak to single peak can be used as a signature to identify abnormal cardiac events. These plots, along with other plots and parameter values ​​described herein, can also be tracked over time before, after, and during treatment to provide information to clinicians and other interested users. System and method for assessing coronary flow reserve

[0154] The present disclosure relates, in part, to methods and systems suitable for determining a coronary flow reserve value in response to one or more of intravascular pressure and flow data or data otherwise correlated therewith. By using a sensing device (SD), such as a pressure or flow sensor, a coronary flow reserve value can be determined over time using thermal convection data. In parallel with the CFR measurement, a distal pressure value Pd can be obtained by sampling the same sensing device, and the Pd value can be used with a reference pressure to simultaneously determine an FFR value. Using various measurement systems described herein, such as an ICD, CFR, FFR, and other parameters described herein can be processed and displayed. The present disclosure also relates to various user interfaces and associated live and review modes used to display and plot CFR and other values.

[0155] Exemplary sources of pressure data may include pressure sensors, such as electrical or optical pressure transducers. Suitable pressure sensors may be located on, in, or otherwise relative to catheters (e.g., delivery catheters, etc.), intravascular data collection plots, guidewires, and other suitable devices and systems. CFR and FFR values ​​may be determined simultaneously and displayed over time as numerical values ​​or time-varying curves on a GUI, or may be used as inputs to generate other diagnostic data regarding the behavior of the cardiac system.

[0156] In one embodiment, the present disclosure relates to an intravascular data collection method that allows diagnostic data and information to be collected and generated. In one embodiment, the method includes adjusting or optimizing a temperature signal of an intravascular heat convection device when the intravascular heat convection device is at a measurement location of interest, sampling the intravascular heat convection device to obtain a baseline heat convection signal value, and sampling the intravascular heat convection device to obtain a Pd value and a heat convection device value for performing FFR and CFR calculations. Results of the FFR and CFR calculations may be output to a display of a catheterization lab device or other display (e.g., a touch screen device).

[0157] The present disclosure relates, in part, to methods and systems suitable for simultaneously determining one or more coronary flow reserve (CFR) and fractional flow reserve (FFR) values ​​using thermal convection devices, such as intravascular pressure and flow sensors, and an intravascular data acquisition and processing system. Additionally, the present disclosure relates, in part, to determining CFR values ​​using an intravascular probe having a pressure sensor and constant temperature anemometry (CTA) or constant voltage excitation (CVEX) anemometry.

[0158] In one embodiment, the CFR is the ratio of the hyperemic absolute flow rate to the baseline absolute flow rate. Similarly, in one embodiment, the CFVR is defined as the ratio of the hyperemic flow rate to the baseline flow rate. The CFR and CFVR are equal in value. The attached reference to the CFR may be used to implement and display CFVR values ​​as well. Thus, use of the term CFR may be substituted for CFVR herein to describe embodiments and measurements of CFVR, and this is within the scope of the present disclosure.

[0159] A variety of data acquisition and analysis systems are available for obtaining information about the coronary system. Data obtained from the blood vessels using the devices, or derived from intravascular or extravascular measurements associated with the blood vessels, can be analyzed or displayed to provide correlations and extrapolations useful to researchers and clinicians. For example, a variety of measurement systems and intravascular probes are available for determining fractional flow reserve (FFR) and coronary flow reserve (CFR). As described herein, pressure sensor-based devices can be used to obtain one or more CFR measurements in a patient.

[0160] In one embodiment, pressure data (Pd) and thermal convection data are collected using an intravascular data collection probe placed in the patient's artery. Exemplary intravascular data collection probes include catheter-based or catheter-delivered probes, guidewire-based probes, imaging probes, ablation probes, ultrasound probes, interferometric probes, and other suitable data collection probes described herein.

[0161] In particular, pressure sensors can be used to acquire data to measure flow rate, heat convection data, and other cardiac system parameters as described herein. The systems, methods, and devices described herein relate, in part, to heat convection and hot film anemometry techniques, such as constant temperature anemometry (CTA) and constant voltage excitation (CVEX) anemometry in some embodiments. As described in more detail below, pressure sensors allow for intravascular data sampling and the generation of CFR measurements, which are advantages over existing thermodilution techniques.

[0162] In the background, a measurement of coronary flow reserve may be performed using a pressure sensor, e.g., a pressure wire, or other pressure sensor capable of operating as a thermodilution device. As part of the prior art, a CFR value is obtained by injecting a cold saline solution into the coronary artery of interest. Then, using the temperature measurement function of the intravascular pressure sensor, the blood temperature rise time (from the start of the injection of cold saline into the artery until the temperature returns to a certain level) is measured. This rise time can be converted into a CFR value.

[0163] Such conventional thermodilution techniques suffer from a lack of precision and can be tedious to implement. For example, the stated precision of an exemplary conventional thermodilution technique may result in an accuracy of less than ±30% for the CFR value. The procedure is tedious and time consuming, typically requiring multiple injections of saline with specific characteristics to generate sufficient data for the system software to calculate the CFR value.

[0164] Using the measurement systems, methods and devices described and illustrated herein, it is possible to obtain a signal that is a measure of the temperature or power of the pressure sensor chip. The chip resistor is heated with an electric current, generating a certain excess temperature relative to the surrounding fluid (blood). The cooling effect of the blood flow on the chip resistor is measured directly (as a temperature value) or indirectly (as the power required to keep the temperature of the chip resistor stable).

[0165] 11 illustrates an exemplary system 710 suitable for measuring CFR. Additionally, system 710 can be used to simultaneously measure CFR and FFR values. Some non-limiting examples of intravascular data acquisition and analysis system 710 or components thereof can include multi-modal systems such as the RadiAnalyzer, RadiAnalyzer Xpress, Quantien, PressureWire systems (e.g., Aeris 1, Aeris 2, or Certus), Optis systems, combined intravascular imaging and pressure monitoring systems, hemodynamic displays with pressure data input, and the like.

[0166] In one embodiment, a system suitable for performing heat convection CFR measurements, either alone or simultaneously with FFR measurements, such as system 710 of FIG. 11, may include multiple components, such as subsystems and devices. As an example, such a system may include a heat convection device 760. Examples of such heat convection devices may include pressure sensor-based devices, such as those described herein. As a specific example, the heat convection device may include a pressure sensor Aeris unit adapted to facilitate heat convection measurements. Such an Aeris unit may be modified or programmed to use the measurement techniques described herein. In one embodiment, the heat convection device may include a pressure sensor and be sized and configured to measure flow, CFR or FFR, or other cardiac system parameters by measuring distal intravascular pressure and other parameters of interest.

[0167] As shown with respect to system 710 in FIG. 11, an exemplary thermal convection CFR measurement system may include a reference pressure device 765. Using a reference pressure device, it is possible to measure a reference pressure (e.g., aortic pressure in one embodiment). The reference pressure device may include a pressure sensor in the guide catheter or delivery catheter. Such a reference pressure device also receives proximal pressure values, such as aortic pressure values ​​(Pa), and transmits them as input for FFR calculation, as shown in system 710.

[0168] The system may also include a signal processing and display device 730 (e.g., a Quantien system from St. Jude Medical), which wirelessly or wiredly receives pressure and heat convection (flow) data from the heat convection device. The device 730 also receives pressure data from a reference pressure device (e.g., an aortic pressure transducer). Embodiments of the present disclosure relate, in part, to various features of pressure sensing devices, measurement systems, and associated software suitable for determining ratios based on signals sampled from an intravascular data collection probe, such as the probes described and illustrated herein. The device 730 may include a display, such as a touch screen display, or other display, that outputs a GUI with measured CFR, FFR, and other data of interest from the heat convection device 760 and the reference pressure sensor 765 (e.g., an aortic pressure transducer). The heat convection data values, in one embodiment, are temperature values. These values ​​may be generated based on electrical changes triggered in the heat convection device. In one embodiment, the heat convection data values ​​are provided in temperature units, such as °C.

[0169] One example of a sensing device that can be used to perform pressure monitoring, flow monitoring, sampling of intravascular data for CFR measurement, and sampling of intravascular data for FFR measurement is a guidewire-based probe having a semiconductor device that includes components that generate electrical changes in response to pressure changes. The embodiments described herein support methods of determining CFR values ​​using thermal convection devices, as well as various systems and methods of determining or measuring ratios using guidewire-based probes and associated software and electrical components of the data collection and analysis system 710. Wired or wireless probes can be used to transmit Pd, Pa, and thermal convection data from sensors associated with a given probe.

[0170] System 710 may perform measurement calculations based on sampled signals from an intravascular probe, or may receive signals encoding the results of calculations performed using circuitry or processing elements located within the probe (e.g., in the proximal connector of the probe). System 710 may also include software, a control system, and data analysis and display devices and processors suitable for graphically displaying pressure values, FFR values, CFR values, sampled Pa values, sampled Pd values, running averages, and other related values.

[0171] The data collection and analysis system 710 may include a processor, such as a microprocessor, memory, and one or more software modules, circuits, or hardware components (e.g., a CFR hardware component or CFR software module 740). The system 710 may also include an FFR hardware component or FFR software module 750. These components or software routines are configured to receive endovascular data and simultaneously determine CFR and FFR values ​​(if such information is selected to be displayed on the interface screen). The CFR hardware or software module may include one or more of the methods and associated empirically determined functions or mathematical relationships described herein for determining CFR values ​​using data sampled from a sensing device (SD), such as the thermal convection device described for the guidewire-based probes that sense temperature and flow.

[0172] In one embodiment, the heat convection data is the relative temperature change of a heated measurement resistor, which is a measure of the flow change around the resistor / device. Further details regarding systems that can be used to obtain heat convection data, and heat convection devices based on pressure and flow sensing devices, are described and illustrated herein.

[0173] The CFR measurement is performed in parallel with the FFR measurement. For example, the CFR measurement software may be implemented as one or more software routines or methods as an extension of the pressure sensor signal processing software and / or one or more software components operating in the hardware components and devices of the system of FIG. Measurement procedure for FFR data and thermal convection CFR data

[0174] An exemplary sequence of steps for a procedure for simultaneous measurement of FFR and thermal convective CFR is described with respect to Figure 12B. These steps may be performed using the system of Figure 11 and systems described herein. Relevant screens of a graphical user interface associated with diagnostic data output are shown in Figures 13A-13D and 5A-5D.

[0175] 12B illustrates an exemplary series of method steps that may be performed to determine one or more CFR values ​​and one or more FFR values ​​for a patient. Steps 10 through 55 may not all be performed in some embodiments. Additionally, some steps may be performed in a different order or simultaneously with other steps.

[0176] As part of the method, a step is performed to set a baseline or otherwise set a zero value for the pressure signal of the sensing device (SD) (e.g., intravascular pressure in saline or another buffer in the tray) (step 10). A step is performed to advance the SD to the catheter opening (but not into the bloodstream) (step 15). A step is performed to set a baseline (zero value) for the SD temperature signal (step 20). A step is performed to advance the SD to a position distal to the catheter opening such that the SD pressure signal (Pd) is equal to the aortic pressure (Pa) signal (step 25). A step is performed to advance the SD to a position to assess the CFR and FFR (step 30). A step is performed to calibrate (adjust) the temperature signal with audio and / or visual feedback to find a maximum, minimum, or other level (step 35). This calibration or adjustment step may be performed in software or may be software facilitated to notify the operator by visual or audio cues when a calibrated state occurs as the control is adjusted to find the temperature signal level. In one embodiment, adjusting or calibrating refers to physically moving the intravascular device radially within the blood vessel to position the intravascular device for an optimal flow level or other desired flow level. The optimal flow rate is typically identified by the temperature signal settling at a maximum or minimum level. The temperature signal level is adjusted to achieve a relative maximum or minimum or other threshold value.

[0177] Continuing with reference to the method depicted in FIG. 12B, the method may also include the steps of initiating a data recording session of SD values ​​and establishing a CFR baseline (step 40). In one embodiment, once the CFR measurements have been obtained, a step of inducing hyperemia is performed (step 45). Thus, in step 45, by way of example, a hyperemic agent such as adenosine is administered to the patient being monitored to determine the CFR and FFR values. A step of verifying that the pressures are equalized and the flow signal has returned to baseline is performed (step 50). Finally, in one embodiment, a step of terminating or aborting the data recording session is performed (step 55) once the desired set of sampled probe values ​​has been obtained or once a concurrent diagnosis or concurrent treatment has been completed. In one embodiment, the baseline level is Level 1 or another established baseline value.

[0178] A graphical user interface (GUI) for an FFR measurement system (such as the Quantien system or the system of FIG. 11) may incorporate one or more processors or control systems that provide user controls for zeroing the pressure sensor temperature signal. Additionally, such user controls may be used to set CFR baseline values, as well as new graph windows for signal conditioning and CFR tracking. The system is also extended with an audio interface / speaker for audio conditioning steps.

[0179] In the various screen shots, one or more areas or panels of the GUI or other display output of the system of FIG. 11 or other systems described and illustrated herein display measurements recorded to simultaneously assess FFR and CFR. For example, the simultaneous display of FFR and CFR data is indicated by Fv / Fv-B (ratio of flow rate / baseline flow rate), which is the result of the CFR calculation, which is displayed along with the FFR value in review mode in the various interface views.

[0180] The present disclosure includes, in part, various features that present advances and new diagnostic information and methodologies regarding CFR and FFR to a user. One such feature is a process for determining a CFR value based on the relationship CFR=b^((x_hyperemia-x_baseline) / c). Additionally, this CFR relationship may be evaluated based on a pressure sensor temperature or power signal measured with an intravascular pressure probe as described herein. As noted herein with respect to FIG. 11, to facilitate simultaneous measurement of FFR and CFR and subsequent display of FFR and CFR values, it is advantageous to perform the CFR software method or hardware component 740 in parallel with the pressure sensor pressure signal processing as part of the FFR software method or hardware component 50. The method steps described herein (e.g., with respect to the process flows of FIGS. 12A and 12B), associated user interfaces and plotting of CFR data, and simultaneous plotting of changes in FFR and CFR over time are further features that provide enhanced diagnostic information to a user.

[0181] FIG. 14 shows the results of a CFR measurement performed by a PressureWire Generation 8 unit from St. Jude Medical using thermal convection flow measurements on the Aeris 2 platform against a reference CFR that serves as a known CFR value for comparison. The measurement was performed at three locations in a 3 mm tube, indicated as red (position 1), blue (position 2), and green (position 3). In one embodiment, during the measurement, a PressureWire rotation is performed before each CFR measurement to determine the maximum flow signal level. The results show that all locations have a maximum deviation within 10%, which compares favorably to the 30% tolerance specified for PressureWire CFR measurements by thermodilution. Visual Representation of Intravascular and Other Cardiac System Data

[0182] Various exemplary graphical user interfaces (GUIs) or display outputs are shown in Figures 13A-13D and 15A-15D, which include data sets generated using one or more of the endovascular measurements, e.g., pressure, temperature, flow measurements, or measurements derived therefrom or correlated thereto. In one embodiment, there are multiple modes of output of the endovascular data processing and display system. By way of example, a live mode and a review mode are detailed below. Live Mode - GUI

[0183] 13A illustrates an exemplary GUI 805 in a live mode, where the data being displayed is data being sampled by an intravascular probe and processed by a measurement system, such as system 710 or other ICDs described herein. The GUI is typically displayed on a touch screen, and various elements on the interface may be activated, deactivated, or otherwise interacted with to change the display, calibrate the system, and make other modifications. In the illustrated live mode, real-time data curves and numerical values ​​are displayed, which provide a real-time perspective to a user reviewing such data, which may be done, for example, before, during, or after a diagnostic procedure of another treatment.

[0184] As shown in FIG. 13A, various graphs and plots can be displayed for the cardiac data being measured. The upper graph window displays the phasic Pd (using one color, such as green, or a second indicia), Pa (using another color, such as red, or a first indicia), and their respective average values. The white phasic curve 807 is the heat convection (flow) data, which is mapped to the current flow ratio value (see Numerical Information below). The average value of the phasic curve matches the current flow ratio value (1.88). The lower graph window displays a colored line 808 (e.g., a yellow line or another indicia) representing the current Pd / Pa value (0.98). The right panel displays the following numerical information from top to bottom: Average Pa. Maximum and minimum Pa values ​​are also shown in small numbers. The average Pd value. The maximum and minimum Pd values ​​are also shown as small numbers. · Pd / Pa values, based on average values ​​of Pd and Pa. Fv / Fv-B (flow rate / flow rate baseline ratio), which is the result of the CFR calculation. In one embodiment, this value is not referred to as CFR in live mode because the definition of CFR is the ratio of flow to baseline flow at maximal hyperemia. These definitions may be modified and changed based on the expectations of the user of the system. In one embodiment, maximal hyperemia exists only for a short period of the measurement cycle. In one embodiment, Pd / Pa is not identified as FFR in live mode.

[0185] The GUI of FIG. 13A includes various user control buttons, namely, "Record", "Equalize", "Patient", "Live", "Review", and "Archive" buttons and menus. The example GUI 805 of FIG. 13A also includes a new control and button for a "CFR Enable" control interface. The "CFR Enable" control is user adjustable to enable or disable FFR+CFR mode. That is, the user can select between FFR mode or FFR+CFR mode. The GUIs illustrated herein are implemented using a touch screen or other control means and input devices in various embodiments.

[0186] The "Baseline" control (shown in FIG. 13A) allows the user to open a new menu where the user can select "Adjust" or "Set Baseline". The "Adjust" control then allows the user to activate an adjustment of the heat convection signal, giving the user the opportunity to optimize the heat convection signal using both visual (graph) and auditory (audio) information, i.e., to place the device at an optimal location within the vessel. The "Set Baseline" control allows the current average value of the heat convection signal to be used as the T for CFR calculation. bas This allows the software to be instructed to store the Review Mode

[0187] In review mode, shown in Figures 13B, 13C, and 13D, a measurement record is displayed. The screen shows the pressure and flow ratios starting at 1 (baseline flow) and then shifting to their respective hyperemia levels (i.e., pressure ratio around 0.8 and flow ratio 5.0 in the case of Figure 13B) at the onset of hyperemia. Note that the scale of the flow ratios is shown on the right side of the upper graph window and ranges from 0.0 to 10.0. In the "review" screen, each ratio is referred to as the FFR and CFR, and the user is to identify maximum hyperemia (where the two ratios become the FFR and CFR) by sliding the cursor from one end of the record to the other. Calculate CFR - Heat Convection Data

[0188] As described herein, some possible transfer functions from blood flow values ​​to the measured pressure sensor signal are listed. In one embodiment, a transfer function of the form x=a+c×logbQ is used, where the base of the logarithm b is unspecified, x is the measured pressure sensor temperature signal or chip power, a is an offset value, c is a gain factor, and Q is the blood flow value. Both a and c depend on the position of the pressure sensor chip in the blood vessel. The inverse of this function, Q=b̂((xa) / c), is used to calculate the flow value from the measured pressure sensor signal. The CFR (Q_hyperemia / Q_baseline) may then be calculated as b̂((x_hyperemia-x_baseline) / c), as further detailed herein. In one embodiment, the offset value (a) is not required for the calculation of the CFR.

[0189] The CFR calculation is done using one of the transfer functions mentioned above, i.e.

number

number

number

[0190] By inserting equation (2) into equation (3), we obtain the following equation.

number

[0191] However, T hyp is the measured temperature at hyperemic flow, and T bas is the measured temperature at baseline flow. For this, the thermal convection device must remain stable at the particular measurement location at both baseline and hyperemic flow (otherwise the constants a and c will not be valid for both hyperemic and baseline). Hyperemia can be visualized in Figures 15A-15D as a negative plateau shown in the lower window of the FFR data plot, and a positive plateau shown for the plot of Fv / Fv-B (flow / flow baseline ratio) in the middle of the screen (see Figure 15A). The vertical line in the left third of the screenshot in Figure 5A represents the onset of hyperemia. Simplifying equation (4) using the logarithmic rule gives:

number

[0192] Further simplification gives the final CFR function used in the CFR calculation software:

number

[0193] Note that the constant a is not necessary for the calculation of the CFR. However, the constant c is very important and is specific to the thermal convection device and to the device's location within the vessel. Also, the CFR value is the ratio of flow to baseline flow, which is the ratio of T during each CFR calculation. bas The value is meant to act as a constant. bas The value of is indirectly given by the user. That is, when the coronary blood flow is at the resting level and the operator places the heat convection device in the optimal measurement position, the “Baseline setting” button on the GUI is pressed, and the software sets the heat convection value (average value) at that time as T bas Store it as.

[0194] This function can be written in a more general form by using an arbitrary logarithm base (b) rather than the natural logarithm base (e), as follows:

number

[0195] Intravascular data collection devices can be used within a blood vessel to generate and receive signals that contain diagnostic information relative to the blood vessel. Such devices may include, but are not limited to, imaging devices, such as optical or ultrasound probes, pressure sensor devices, and other devices suitable for collecting data about blood vessels or other components of the cardiovascular system.

[0196] The present disclosure relates, in part, to an intravascular data collection system and associated methods used to transform or analyze intravascular data collected by an intravascular probe in a processor-based system. The results of such analysis and transformation may be displayed to an end user in a variety of representations, such as by a display in communication with or part of a system, such as a pressure monitoring system or an intravascular data collection system. Examples of such systems are shown, for example, in Figures 1A-2B, 5A-5E, 11, 13A-13D, 15A-15D, and in other figures, in whole or in part, in different formats.

[0197] In one embodiment, a display console is used to display a user interface, e.g., a touch screen interface, and one or more of flow rate, maximum flow rate, minimum flow rate, flow rate threshold, relative extremes of flow rate, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, and one or more myocardial resistance index (IMR) values ​​on one or more panels or user interface areas, or, in one embodiment, as values ​​or plots or graphs on components of the system. The display device, console, or a cart or other housing to which they are attached or in electrical or wireless communication may include one or more microprocessors for performing one or more of the steps described herein and for processing intravascular signals from the probes described herein.

[0198] These diagrams and user interface screens may be used as diagnostic tools in conjunction with intravascular or angiographic images to inform stenting decisions, identification of areas of diagnostic interest, and other cardiac treatment decisions.

[0199] In one embodiment, a user of the systems, methods, and displays disclosed herein can review a display of the FFR and CFR values ​​provided over time before, during, or after a procedure to diagnose the severity of the stenosis, identify the location of the stenosis, guide a course of treatment, assess the effectiveness of treatment, and assess the need for further treatment after a procedure. Embodiments of Flow Peak / Flow Threshold Measurement and Assessment

[0200] The pressure or flow sensor or other sensing device may be used in combination with a system, such as an integrated cardiology display system or other systems described herein, to determine one or more categories of intravascular data over time using thermal convection or flow data acquired using the flow sensor or from other measurements correlated with the flow data. In addition to thermal convection sensors, mechanical, optical, or other flow sensors may be used. The system may include signal processing and display devices (e.g., RadiAnalyzer system, RadiAnalyzer Xpress system, Quantien system, Aeris system, Prestige guidewire-based probe system, ComboMap® pressure and flow system, and other devices and systems that sense intravascular pressure or determine FFR). In one embodiment, a pressure or flow sensor is used that is part of an intravascular probe. The system may also include or be in communication with a reference pressure device, such as a catheter suitable for measuring proximal or distal pressure values. The reference pressure device may be used to measure a reference pressure (e.g., aortic pressure in one embodiment). The reference pressure device may include a pressure sensor in the guide catheter or the delivery catheter.

[0201] By sampling the same sensing device, a distal pressure value Pd can be obtained, which can be used in conjunction with the reference pressure to simultaneously determine the FFR value. Such a reference pressure device also receives proximal pressure values ​​(Pa), such as aortic pressure values, and transmits these to a suitable system, such as the systems described herein and illustrated in the exemplary embodiments of Figures 1A-2B, 5A-5E, 11, 13A-13D, and 15A-15D, for subsequent analysis and calculation.

[0202] In one aspect, the disclosure relates to detecting a flow threshold using intravascular data acquired by one or more of the techniques described herein, including, but not limited to, a flow peak or other relative extreme, an inflection point, a first derivative, or a second derivative during a cardiac cycle. The detected flow threshold, e.g., the flow peak (or other value or time point), may then be selected as an index for the measurement system and used, for example, to calculate pressure ratios and pressure differences. Exemplary processing steps are described in further detail with reference to FIGS. 16, 17A, and 17B, and with reference to exemplary pressure and flow curves and plots of Pa and Pd values ​​for each cardiac cycle.

[0203] Embodiments of the present disclosure relate in part to various features of pressure sensing devices, measurement systems, and associated software suitable for determining the ratio based on signals sampled from an intravascular data collection probe. These signals may be various values, such as a pressure or flow threshold (specified by the user via an interface or automatically determined by the measurement system) used to select a time point or period during the cardiac cycle. This time point may be the maximum of a series of flow values ​​acquired by the probe. The selected time point or period is used to perform a measurement or to select an already acquired measurement, including distal pressure values ​​or other parameters, including but not limited to flow velocity, maximum flow rate, minimum flow rate, flow rate threshold, relative extremes of flow rate, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, and one or more myocardial resistance index (IMR) values. The flow threshold may be specified as a level above which a measured level of flow is classified as peak flow or high flow.

[0204] Alternatively, a maximum flow value or absolute value of the flow measurement may be identified as a flow threshold or peak flow value, and one or more pressure values ​​or other intravascular parameters of interest are measured at that point in the cardiac cycle. Selection of a flow threshold allows the sensing device to obtain a relative pressure differential, flow value, or other value (e.g., a statistical value or other indicator) relative to that point in time as described herein. Diagnostic data collected at each flow threshold (e.g., peak flow, maximum flow, etc.) may be displayed as a value, plotted or otherwise processed, and used to generate a correlation value, which may also be displayed or plotted.

[0205] Described herein are diagnostic methods and associated thermal convection systems and devices suitable for assessing stenosis of coronary arteries. Using the systems and methods, it is possible to detect flow peaks (or other values ​​or points as described herein) that can identify points or events of interest during the cardiac cycle. These points or events may be used as references for measuring pressure ratios or pressure differentials at those events or points. The methods and systems can be used to perform non-hyperemic measurements, such as measuring non-hyperemic or resting FFR values.

[0206] Some current techniques for determining FFR independent of flow data or other indices associated with flow peaks or other times during the cardiac cycle assume that the FFR value is determined by explicitly defining regions where high flow always occurs. Unlike such restrictive techniques that simply specify such regions to be selected for data collection, the flow velocity or other flow measurement based systems and methods described herein are capable of accurately measuring high or peak flow when they occur, or other indices that correlate with or are derived from such flow measurements. In some embodiments, the peak flow referred to herein may correspond to the occurrence of maximum blood flow, which is associated with the maximum blood flow peak or other relative extreme during the cardiac cycle.

[0207] A point of interest (at a flow threshold such as the maximum blood flow peak) can always be found and the pressure drop measured at that point in the cardiac cycle. The occurrence of the flow peak can be located anywhere in the cardiac cycle, so the cycle ratio is not determined by preselecting a region based on expectations regarding the behavior of the heart in systole and diastole. The pressure drop can be measured at rest or / and during hyperemia. The occurrence of the flow peak can be located anywhere in the cardiac cycle and the ratio of distal pressure (Pd) to aortic pressure (Pa) can be measured at this point (or at several points / samples in the vicinity of this point). If the pressure drop is of interest, the difference (Pa-Pd) is measured at the same one or more points. As shown in FIG. 18, the aortic pressure (P 大動脈) curve has the Pa value at the peak flow of the cardiac cycle shown, and the Pd value at the vertical double arrow. By finding and using these values, it is possible to calculate FFR, pressure difference, and other values ​​for each cardiac cycle at the peak flow or other specified flow threshold. In one embodiment, an arithmetic mean or other statistical or data measure (mean, median, mode, standard deviation, etc.) of the measurements over several heart rates is calculated. This ratio is the Pd / Pa at the flow peak or other flow threshold. This is the minimum Pd / Pa during the cardiac cycle at baseline (when hyperemia is not induced) and represents the non-hyperemic resting index.

[0208] FIG. 16 is a sequence of method steps for a diagnostic method, such as a method for evaluating a blood vessel or stenosis, using flow thresholds and other measured intravascular parameters. As a step of the method, a flow threshold is detected using an interface or other intravascular measurement system and one or more sensing devices in a non-hyperemic (or hyperemic) state (step A1). As a result, the sensing device or system component may output one or more peak flow values ​​(or other identified value(s)) (step A2). Additionally, the system and associated control logic may determine a pressure ratio and / or pressure difference in response to or upon the occurrence of the identified peak flow values ​​(or other identified value(s)) (step A3). Using such pressure ratios or pressure differences, the system may generate a statistical or other indicator (e.g., arithmetic mean, mode, deviation, or other indicator or statistic) of the pressure ratio, pressure difference, or both, over one or more heartbeats (step A4).

[0209] The system may then display or output diagnostic information (step A5), such as a plot or ratio or difference obtained at a flow threshold such as peak flow or maximum flow. Flow values ​​may be generated using an intravascular sensor and may be used to provide input to the system for selecting a flow threshold. The system may display one or more values ​​of pressure ratio (Pd / Pa) or values ​​correlated therewith at an identified value such as maximum flow or other identified value (step A6). The system may display / categorize the output as non-hyperemic resting baseline if data was collected in a non-hyperemic state (step A6-1). The system may display / categorize the output as hyperemic data if hyperemic agents were used (step A6-2). Additionally, the system may display one or more values ​​of pressure difference at an identified value such as maximum flow or other identified value (step A7). The system may display / categorize the output as non-hyperemic resting baseline (step A7-1). The system can display / classify the output as hyperemic data (step A7-2).

[0210] FIG. 17A is another embodiment of a diagnostic method related to a pressure value ratio suitable for use with one or more of the pressure and flow sensing systems described herein. In FIG. 17A, as shown, various steps related to a Pd / Pa ratio are outlined. The system is first used to transmit / provide intravascular data for a vessel of interest (step B1). Next, a step of determining a first flow value at a first flow threshold during a first time period or cardiac event (step B2) is performed. A step of determining a ratio of distal pressure to aortic pressure (pd / pa) during a first flow threshold (step B3) is performed. Furthermore, the system may be set up for a step of determining one or more indices related to the pressure ratio over multiple time periods or cardiac events (step B4). The system can then display one or more of pd / pa, the determined indices, the determined flow value, or values ​​derived therefrom, either numerically or as a plot against time or for each cardiac event (step B5). FIG. 18 is a representation of an exemplary result of the method of FIG. 17A, showing a plot suitable for showing flow thresholds and the Pa and Pd values ​​found at such thresholds, with the Pa and Pd values ​​shown, for example, along vertical line A in the first cardiac cycle A.

[0211] FIG. 17B is another embodiment of a diagnostic method related to a pressure value ratio suitable for use with one or more of the pressure and flow sensing systems described herein. In FIG. 17B, various steps of a diagnostic method related to a pressure difference between an intravascular pressure value and another pressure value of interest are outlined. The system may be used to perform a step of transmitting / providing intravascular data related to the vessel of interest (step B1). In another step, a step of determining a first flow value at a first flow threshold during a first period or cardiac event (step B2) may be performed. Flow values ​​measured with a flow sensor described herein (e.g., using temperature and voltage) may be used to select the flow threshold at which measurements are taken. A step of determining a pressure difference between aortic pressure and distal pressure (pa-pd) during a first flow threshold (step C1) may be performed.

[0212] As a further step, a step of determining one or more indices relating to pressure differences over multiple periods or cardiac events (step C2) may be performed, for example by user selection or by predefined selection in the system. The system displays one or more of the determined indices, the determined flow values, or values ​​derived therefrom, either numerically or as a plot against time or for each cardiac event (step C3). Figure 18 shows an exemplary display of the results of the method of Figure 17B.

[0213] Referring to FIG. 18, two plots or traces are generated using the measured intravascular data (e.g., by one or more of the methods of FIG. 16, FIG. 17A, and FIG. 17B). Plot 910 (top of the figure) and plot 920 (bottom of the figure) show pressure and flow values ​​versus time, respectively, for cardiac cycles A-E. That is, a series of pressure curves over time over multiple cardiac cycles are shown. In the top diagram, plot 910, the solid line corresponds to the upper curve and shows the aortic pressure rising and falling with time as the heart goes through a series of cardiac cycles. The lower pressure curve corresponds to the distal pressure measured within the vessel, shown by the dotted lines 100A, 100B, 100C, 100D, and 100E, which correspond to flow thresholds. The Pd and Pa values ​​can be found at the intersection of the double-headed arrows and can be used to determine a first parameter, such as Pd-Pa or Pd / Pa, or a second parameter that is otherwise correlated with the first parameter.

[0214] Each of the vertical dotted lines labeled A through E indicates a flow threshold at which data is collected and diagnostic data is refined for each cardiac cycle. The illustrated vertical lines correspond to a maximum flow rate. However, other flow thresholds may be used, for example, X% of the maximum flow rate. X ranges from about 1 to about 100. There are five cardiac cycles illustrated, A through E. The pressure differences indicated by the double-headed arrows and identified as PD-A, PD-B, PD-C, PD-D, and PD-E are the pressure differences or pressure ratios determined at the associated time slices indicated by the vertical dotted lines corresponding to the flow thresholds selected in the system. As indicated herein, the maximum or peak flow rate was the basis for the flow thresholds used to determine where to measure the pressure ratio or pressure difference. The flow thresholds indicated by the vertical lines may be selected as the maximum flow value for each cycle, which may be determined using temperature-based flow measurements or other flow sensors as described herein.

[0215] For the five heartbeats shown, the vertical double arrows correspond to the difference between the first and second pressures. These double arrows align with the vertical dotted lines that span the top view and continue to the bottom view. These dotted lines indicate the occurrence of flow thresholds, such as peak flow. These dotted lines may be set using the control system and other flow thresholds of interest (e.g., flow measurements or other correlated values). Diagnostic values ​​or plots thereof that may be determined and displayed at flow thresholds include, but are not limited to, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, and one or more myocardial resistance index (IMR) values.

[0216] The various pressure differences and pressure problems described herein may be displayed as numerical values ​​for use in diagnostic or other procedures. These differences and ratios may be used to generate various indices, such as statistics and other indices. Examples of such statistics include weighted averages, means, arithmetic means, modes, medians, standard deviations from baseline parameters (whether hyperemic or non-hypemic), and other statistics related to endovascular and coronary system parameters. Non-limiting software features and embodiments for implementing pressure and flow related data collection and analysis methods and systems

[0217] The following description is intended to provide a general overview of device hardware and other operating components suitable for performing the disclosed methods described herein. This description is not intended to limit the applicable environment or scope of the present disclosure. Similarly, the hardware and other operating components may be suitable as part of the above-described devices. The present disclosure may also be implemented in other system configurations, such as personal computers, multiprocessor systems, multiprocessor-based or programmable electronic devices, network PCs, minicomputers, mainframe computers, and the like. The present disclosure may also be implemented in distributed computing environments, where tasks are performed by remote processing devices (e.g., in different rooms of a catheterization lab) that are linked through a communications network.

[0218] Some portions of the detailed description are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory. These algorithmic descriptions and representations are within the capabilities of those skilled in the art of computers and software. In one embodiment, an algorithm is here, and generally, conceived to be a self-consistent sequence of operations leading to a desired result. The operations performed as method steps, or other forms described herein, require physical manipulations of physical quantities. Usually, although not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, transformed, compared, and otherwise manipulated.

[0219] As will become apparent from the description below, unless otherwise indicated, throughout the description, references to words such as "processing" or "computing" or "retrieving" or "detecting" or "measuring" or "calculating" or "comparing" or "generating" or "sensing" or "seeking" or "displaying" or operations related to Boolean logic or other sets, etc., should be understood to mean computer system or electronic device operations or processing that manipulates data represented in physical quantities (electronic quantities) in the registers and memories of the computer system or electronic device, or converts it into other data that is similarly represented as physical quantities in electronic memories or registers or other such information storage devices.

[0220] In some embodiments, the disclosure also relates to apparatus for performing the operations described herein. The apparatus may be constructed specifically for the required use, or may comprise a general-purpose computer selectively activated or reconfigured by a computer program stored in the computer. Various circuits and circuit components may be used to perform some of the data collection and transformation and processing described herein.

[0221] The algorithms and displays presented herein are not inherently related to any particular computer or other apparatus. Various general-purpose systems may be used with programs in accordance with the teachings herein, or it may prove convenient to construct more specialized apparatus to perform the required method steps. The required structure for a variety of these systems will appear from the description below. In addition, the description of this disclosure is not directed to any particular programming language, and thus various embodiments may be implemented using a variety of programming languages.

[0222] The embodiments of the present disclosure may be implemented in a variety of forms, including, but not limited to, computer program logic used in conjunction with a processor (e.g., a microprocessor, microcontroller, digital signal processor, or general purpose computer), programmable logic used in conjunction with a programmable logic device (e.g., a field programmable gate array (FPGA) or other programmable logic device), discrete components, integrated circuits (e.g., an application specific integrated circuit (ASIC)), or any other means including any combination thereof. In an exemplary embodiment of the present disclosure, some or all of the processing of data collected using the OCT probe and processor-based system is implemented as a set of computer program instructions, which are converted into a computer-executable form, stored in such form on a computer readable medium, and executed by a microprocessor under the control of an operating system. Thus, the queries, responses, transmitted probe data, input data, and other data and signals described herein are converted into processor understandable instructions suitable for generating pressure and flow data, detecting stenosis, determining maximum flow values, calibrating using a CVEX-based transfer function, calibrating using a CTA-based transfer function, determining maximum flow values, determining CFR values, determining FFR values, displaying and plotting the data and parameters described herein in areas of the GUI, or otherwise performing analysis and comparisons of pressure vs. flow curves and flow measurements, and other features and embodiments described above. Data and parameters suitable for display as plotted curves, values, or other representations in a graphical user interface may include, but are not limited to, fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, flow thresholds, mean flow thresholds, and myocardial resistance index (IMR) values.

[0223] Computer program logic implementing all or part of the functionality previously described herein may be embodied in various forms, such as, but not limited to, source code form, computer executable form, or various intermediate forms (e.g., forms generated by an assembler, compiler, linker, or locator). Source code may include a series of computer program instructions implemented in any of a variety of programming languages ​​(e.g., object code, assembly language, or high-level languages ​​such as Fortran, C, C++, JAVA, or HTML) for use with a variety of operating systems or operating environments. The source code may define and use various data structures and communication messages. The source code may be in a computer executable form (e.g., by an interpreter) or the source code may be converted into a computer executable form (e.g., by a translator, assembler, or compiler).

[0224] The computer program may be stored in any form (e.g., source code form, computer executable form, or intermediate form) on a permanent or temporary tangible storage medium, such as a semiconductor memory device (e.g., RAM, ROM, PROM, EEPROM, or flash programmable RAM), a magnetic memory device (e.g., diskette or fixed disk), an optical memory device (e.g., CD-ROM), a PC card (e.g., PCMCIA card), or other memory device. The computer program may be stored in any form in a signal capable of being transmitted to a computer using any of a variety of communication technologies, including, but not limited to, analog, digital, optical, wireless (e.g., Bluetooth), networking, internetworking, and the like. The computer program may be distributed in any form, such as on a removable storage medium (e.g., shrink-wrapped software) accompanied by printed or electronic documentation, or may be preloaded into a computer system (e.g., on a system ROM or on a fixed disk), or may be distributed from a server or bulletin board via a communications system (e.g., the Internet or World Wide Web).

[0225] Hardware logic (including programmable logic for use in conjunction with a programmable logic device) implementing all or a portion of the functionality previously described herein may be designed using traditional manual techniques or may be designed, captured, simulated, and electronically documented using a variety of tools, such as computer-aided design (CAD), hardware description languages ​​(e.g., VHDL or AHDL), or PLD programming languages ​​(e.g., PALASM, ABEL, or CUPL).

[0226] The programmable logic may be stored in a tangible storage medium, either permanently or temporarily, such as a semiconductor memory device (e.g., RAM, ROM, PROM, EEPROM, or flash programmable RAM), a magnetic memory device (e.g., diskette or fixed disk), an optical memory device (e.g., CD-ROM), or other memory device. The programmable logic may be stored in a signal that can be transmitted to a computer using any of a variety of communication technologies, including, but not limited to, analog, digital, optical, wireless (e.g., Bluetooth), networking, and internetworking technologies. The programmable logic may be distributed on a removable storage medium (e.g., shrink-wrapped software) accompanied by printed or electronic documentation, or may be preloaded into a computer system (e.g., on a system ROM or fixed disk), or may be distributed from a server or bulletin board via a communication system (e.g., the Internet or World Wide Web).

[0227] Various examples of suitable processing modules are described in detail below. In this specification, a module refers to software, hardware, or firmware suitable for performing a specific data processing or data transmission task. Typically, in a preferred embodiment, a module refers to a software routine, program, or other memory resident application suitable for receiving, converting, routing, and processing instructions or various types of data, such as resistance changes, guidewire probe data, temperature data, intravascular flow data, intravascular pressure data, transfer function output calibration data, excitation voltage, and other information of interest.

[0228] The computers and computer systems described herein may include operatively associated computer-readable media, such as memory that stores software applications used to acquire, process, store, and / or communicate data. It will be understood that such memory may be internal, external, remote, or local to the computer or computer system with which it is operatively associated.

[0229] Memory may include any means for storing software or other instructions, such as, but not limited to, a hard disk, an optical disk, a floppy disk, a DVD (digital versatile disk), a CD (compact disk), a memory stick, flash memory, a ROM (read only memory), a RAM (random access memory), a DRAM (dynamic random access memory), a PROM (programmable ROM), an EEPROM (extended erasable programmable read only memory), and / or other similar computer readable medium.

[0230] In general, computer readable memory media applied in connection with the embodiments of the disclosure described herein may include any memory medium capable of storing instructions executed by a programmable device. Where applicable, the method steps described herein may be implemented or performed as instructions stored in one or more computer readable memory media. These instructions may be software implemented in various programming languages, such as C++, C, Java, and / or various other types of software programming languages ​​that may be applied to form instructions according to the embodiments of the disclosure.

[0231] A storage medium may be non-transient or may include a non-transient device. Thus, a non-transient storage medium or a non-transient device may include a device that is tangible, which means a device that has a concrete physical form, but whose physical state may change. Thus, for example, non-transient means that the device remains tangible despite such state changes.

[0232] The aspects, embodiments, features, and examples of the present disclosure are to be considered in all respects as illustrative and are not intended to limit the disclosure, the scope of which is defined solely by the claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art that do not depart from the spirit and scope of the present disclosure as claimed.

[0233] The use of headings and sections in this application is not intended to limit the disclosure, and each section may apply to any aspect, embodiment, or feature of the disclosure.

[0234] Throughout this application, wherever a composition is described as having, including, or consisting of particular components, or wherever a process is described as having, including, or consisting of particular process steps, it is contemplated that the composition of the present teachings also consists essentially of (or consists of) the recited components, and that the process of the present teachings also consists essentially of (or consists of) the recited process steps.

[0235] When an element or component is described in this application as being included in and / or selected from a list of described elements or components, it is understood that the element or component can be any one of the described elements or components and can be selected from a group consisting of two or more of the described elements or components. Further, it is understood that the elements and / or features of the compositions, devices, or methods described herein can be combined in various manners without departing from the spirit and scope of the present teachings, whether expressly or implicitly stated herein.

[0236] Use of the words "include," "includes," "including," "have," "has," and "having" should generally be understood to be open-ended and non-limiting, unless otherwise specified.

[0237] The use of the singular term herein includes the plural term (and vice versa) unless specifically stated otherwise. Additionally, the singular forms "a," "an," and "the" include the plural unless the context dictates otherwise. Additionally, when the word "about" is used before a quantitative value, the present teachings also include that particular quantitative value itself unless specifically stated otherwise.

[0238] It should be understood that the order of steps or order for performing certain actions is not important so long as the present teachings remain functional. Moreover, two or more steps or actions may be performed simultaneously.

[0239] When a range or list of values ​​is given, each intermediate value between the upper and lower limits of that range or list of values ​​is considered individually and encompassed within the disclosure as if each value were specifically recited herein. In addition, smaller ranges between and including the upper and lower limits of a given range are also considered and encompassed within the disclosure. The listing of exemplary values ​​or ranges does not disclaim other values ​​or ranges between and including the upper and lower limits of a given range.

[0240] It is understood that the drawings and descriptions of the present disclosure are simplified to describe relevant elements for a clear understanding of the present disclosure, and other elements are omitted for clarity. However, as will be understood by those skilled in the art, these elements and other elements may be desirable. However, because such elements are well known in the art and they do not facilitate a better understanding of the present disclosure, descriptions of such elements are not provided herein. It is understood that each drawing is shown for illustrative purposes and is not shown as a structural diagram. The omitted details and modifications or alternative embodiments are within the purview of those skilled in the art.

[0241] It will be understood that in some aspects of the disclosure, multiple components may be substituted for single components to provide a certain element or structure or to perform one or more desired functions, and multiple components may be substituted for a single component, and unless such substitution is deemed inoperative in practicing a particular embodiment of the disclosure, such substitution is deemed to be within the scope of the disclosure.

[0242] Each example shown in this specification is intended to illustrate a potential and specific embodiment of the present disclosure. Those skilled in the art will understand that these examples are primarily intended to illustrate the present disclosure. There may be variations to these figures or operations described herein without departing from the spirit of the present disclosure. For example, in some cases, method steps or operations may be performed or executed in a different order, or operations may be added, deleted, or modified.

[0243] [Appendix 1] one or more memory devices; a computing device in communication with the memory device, the memory device executable by the computing device, determining one or more intravascular pressure values ​​in response to a first electrical signal from a measurement circuit formed from the guidewire-based probe and the interface device; determining one or more intravascular flow values ​​using a transfer function in response to a second electrical signal from the measurement circuit formed from the guide wire-based probe and the interface device; and displaying a time-varying pressure vs. flow curve generated based on the one or more intravascular pressure values ​​and the intravascular flow values. Intravascular pressure and flow monitoring system. [Appendix 2] 2. The intravascular pressure and flow monitoring system of claim 1, wherein the pressure versus flow curve is displayed in near real time. [Appendix 3] 2. The intravascular pressure and flow monitoring system of claim 1, wherein the transfer function T(x) is of the form T(x)=a+b×ln(x), where x is the flow rate, and a and b are constants. [Appendix 4] The transfer function T(x) is T(x)=a+b×x c2. The intravascular pressure and flow monitoring system of claim 1, wherein x is the flow rate and a, b, and c are constants. [Appendix 5] 2. The intravascular pressure and flow monitoring system of claim 1, further comprising instructions for displaying one or more cardiovascular-related values ​​obtained during one or more time points. [Appendix 6] 6. The intravascular pressure and flow monitoring system of claim 5, wherein the one or more cardiovascular related values ​​are selected from the group consisting of flow velocity, pressure values, maximum flow rates, minimum flow rates, relative extreme values ​​of flow rates, one or more Fractional Flow Reserve (FFR) values, Coronary Flow Reserve (CFR) values, Coronary Flow Velocity Reserve (CFVR) values, Instantaneous Flow Reserve (IFR) values, and one or more Myocardial Resistance Index (IMR) values. [Appendix 7] 6. The intravascular pressure and flow monitoring system of claim 5, further comprising instructions for displaying one or more trajectories or signatures generated in response to the intravascular probe data for one or more locations within the artery. [Appendix 8] 6. The intravascular pressure and flow monitoring system of claim 5, further comprising instructions for displaying a user interface including flow velocity, pressure values, maximum flow rates, minimum flow rates, relative extreme values ​​of flow rate, one or more fractional flow reserve (FFR) values, coronary flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous flow reserve (IFR) values, or one or more myocardial resistance index (IMR) values ​​generated using the pressure and flow data from the intravascular probe. [Appendix 9] 6. The intravascular pressure and flow monitoring system of claim 5, further comprising instructions for determining one or more temperature values ​​using a linear or other function in response to a second electrical signal from the measurement circuit formed from the guidewire-based probe and the interface device. [Appendix 10] The intravascular pressure and flow monitoring system of Appendix 5, further comprising instructions for calibrating the guidewire-based probe by the following calibration method steps: selecting an excitation voltage for the pressure sensor so that the temperature of the pressure sensor approximately matches the temperature of the blood in which the pressure sensor is placed; determining the absolute temperature of blood in a blood vessel of interest; and using the pressure sensor to measure a flow value in the blood vessel. [Appendix 11] 11. The intravascular pressure and flow monitoring system of claim 10, wherein the step of determining the absolute temperature of blood in the blood vessel of interest includes taking measurements during changes in a switch configuration in an interface system. [Appendix 12] A display system; a pressure and flow measurement system in electrical communication with the display system and including the computing device; the computing device disposed in one of the display system or the pressure and flow measurement system; one or more panels generated using the computing device and rendered on the display, the one or more panels including flow and pressure values ​​obtained using an intravascular probe equipped with a pressure and flow sensor; 6. The intravascular pressure and flow monitoring system of claim 5, further comprising: [Appendix 13] 13. The intravascular pressure and flow monitoring system of claim 12, wherein one or more panels include a pressure versus flow curve, the pressure versus flow curve including one or more trajectories generated using intravascular pressure and flow data, and further includes an input for receiving a data signal from the intravascular probe, the intravascular probe including a temperature sensor for measuring temperature changes that correlate with flow values. [Appendix 14] 13. The intravascular pressure and flow monitoring system of claim 12, wherein the one or more panels include a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of a measurement value, a ratio of a measurement value to a derived value, a ratio of a first derived value to a second derived value, a range, one or more of a fractional flow reserve (FFR) value, a coronary flow reserve (CFR) value, a coronary flow velocity reserve (CFVR) value, an instantaneous flow reserve (IFR) value, and one or more myocardial resistance index (IMR) values. [Appendix 15] and instructions for processing the coronary flow reserve data using an intravascular pressure or flow sensor, the instructions comprising: Sampling an intravascular data collection probe to obtain one or more distal pressure values ​​(Pd) from a distal region of the blood vessel and one or more thermal convection data values; receiving at an intravascular data processing system one or more aortic pressure values ​​(Pa) obtained from a proximal region of the blood vessel; determining one or more fractional flow reserve (FFR) values ​​from the one or more distal pressure values ​​and the one or more aortic pressure values; determining one or more coronary flow reserve (CFR) values ​​from the one or more thermal convection data values; displaying one or more FFR values ​​and one or more CFR values ​​on a display device, each CFR value being determined using a transfer function. 13. An intravascular pressure and flow monitoring system as described in claim 12. [Appendix 16] 16. The intravascular pressure and flow monitoring system of claim 15, wherein the transfer function is of the form T=a+c×lnQ, where T is the measured temperature of the temperature variable resistor of the thermal convection device, Q is the flow rate, and a and c are constants. [Appendix 17] Each CFR value is in the format b

number

Claims

1. 1. A method for intravascular pressure and flow monitoring, comprising: measuring, with one or more sensors, a plurality of intravascular blood flow values, a plurality of proximal pressure values, and a plurality of distal pressure values ​​during each of a plurality of cardiac cycles; determining a plurality of flow thresholds using the plurality of intravascular blood flow values, the flow thresholds including respective flow thresholds for the plurality of cardiac cycles; determining a proximal pressure value (Pa) and a distal pressure value (Pd) at each flow threshold; calculating a first diagnostic parameter based on the Pa and Pd values ​​at each flow threshold; displaying the diagnostic parameters for the plurality of cardiac cycles on a user display; The method includes:

2. The first diagnostic parameter is a pressure difference Pa-Pd at each flow rate threshold, or a pressure ratio Pd / Pa at each flow rate threshold. The method of claim 1.

3. each flow threshold is a flow peak during each of the cardiac cycles, a relative extremum during each of the cardiac cycles, an inflection point during each of the cardiac cycles, a first derivative during each of the cardiac cycles, or a second derivative during each of the cardiac cycles. The method according to claim 1 or 2.

4. The diagnostic parameter is an average value of a pressure difference Pa-Pd at each flow threshold in the plurality of cardiac cycles, or an average value of a pressure ratio Pd / Pa at each flow threshold in the plurality of cardiac cycles.

4. The method according to any one of claims 1 to 3.

5. The diagnostic parameter is an arithmetic mean of pressure differences Pa-Pd at each flow threshold in the plurality of cardiac cycles, or an arithmetic mean of pressure ratios Pd / Pa at each flow threshold in the plurality of cardiac cycles.

4. The method according to any one of claims 1 to 3.

6. the one or more sensors are part of an intravascular guidewire-based probe disposed at a distal end of a guidewire; The one or more sensors include An active resistor that is sensitive to temperature and pressure; a passive resistor that is sensitive to temperature and insensitive to pressure; 6. The method according to any one of claims 1 to 5.

7. The plurality of distal pressure values ​​include processing a first electrical signal associated with the active resistor and the passive resistor; determining the distal pressure value based on the first electrical signal; The method is performed by performing the steps of: The plurality of intravascular blood flow values ​​are processing a second electrical signal associated with the passive resistor; determining the intravascular blood flow value using a transfer function based on the second electrical signal; The method is performed by performing the steps including: The method according to claim 6.

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