Intravascular pressure and flow data diagnostic system, device and method

Abstract

In part, the present invention relates to computer-based methods, devices and systems suitable for performing intravascular data analysis and measurement of various data, such as pressure and flow data. The present invention relates to probes and methods suitable for determining events in the cardiac cycle, such as flow thresholds, such as peak flow, portions thereof, other intravascular parameters or time points during which a change in peak flow or one of these parameters occurs. Exemplary probes include one or more of pressure sensors, resistors, flow sensors, and can be used to generate diagnostic data based on measured intravascular parameters and other parameters. In part, the present invention relates to methods and systems suitable for determining coronary flow reserve values ​​in response to one or more of intravascular pressure and flow data or data otherwise related thereto.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 61 / 975,424 filed on April 4, 2014 and U.S. Provisional Patent Application No. 62 / 073,284 filed on October 31, 2014, the entire disclosures of which are incorporated herein by reference. Technical Field

[0003] The present invention relates generally to intravascular measurements, such as pressure, temperature and flow measurements, and related diagnostic methods and apparatus. Background Art

[0004] The sensor and guidewire assembly can be used to collect intravascular data using a measurement sensor located at or near its distal end. These devices are commonly used in applications that measure the internal properties of tissues and fluids (such as blood pressure). The sensor and guidewire assembly can be introduced into an artery, vein, or other human organ by itself or through a catheter that is already in the patient. These assemblies can be used to measure pressure and other parameters.

[0005] For example, such components can be used with one or more pressure sensing devices (such as a delivery catheter) to measure fractional flow reserve (FFR) using pressure data. In addition, coronary flow reserve (CFR) measurements can be performed using a thermodilution-based method. In such methods, a CFR value is 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 the injection of the cold saline solution into the artery until the temperature returns to a specific level.

[0006] Thermodilution has a number of constraints. The calibration accuracy of the method is as low as + / -30%. In addition, the process is cumbersome / time consuming, requiring multiple injections of a specific amount of saline to generate enough data for the system software to calculate the CFR value. Given the nature of the required thermodilution system, saline delivery, and subsequent measurements, FFR and CFR are performed as two separate methods.

[0007] FFR is used to provide a measure of the severity of stenosis in a coronary artery. The typical method of determining FFR is to measure the pressure drop in the coronary arteries during hyperemia. Hyperemia-inducing substances are injected to cause an increase in blood flow in the coronary system for a controlled period of time. The pressure drop is measured during this period and used as an input in determining FFR.

[0008] In part, the present invention is directed to methods, systems, and apparatus suitable for measuring FFR, CFR, and other values ​​and generating diagnostic outputs that overcome some of the challenges of existing approaches. Summary of the invention

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

[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. In addition, at least one of the first resistor and the second resistor is also pressure sensitive. The sensor can be delivered with the aid of a guidewire and can be used to measure pressure before and after a candidate stenosis while simultaneously obtaining flow data, pressure data, or temperature data based on changes in excitation voltage, current, temperature, or other sensor parameters. Various control systems and calibration methods can be used to support such pressure and flow measurements.

[0011] In one embodiment, the present invention relates to the use of a digital control system while performing simultaneous pressure and flow measurements using a semiconductor-based pressure sensor. The digital control system overcomes certain deficiencies of analog control systems. Specifically, some advantages of digital control systems include calibration features and user-specified temperature selection features. Digital systems can also be used to improve signal-to-noise levels. The calibration feature includes reading information digitally encoded on a storage device associated with a given sensing probe, and adjusting the control system level in response thereto. The storage device can be attached to the probe, such as a PROM, EEPROM, RFID or other suitable storage device.

[0012] The temperature selection feature includes automatically obtaining the temperature of the blood vessel using one or more sensors and then changing the electrical properties of the sensing system. This change in current, voltage, impedance or other parameters is in response to a user-specified temperature above the temperature of the flowing blood, such as an overtemperature or sensing temperature range. The overtemperature or sensing temperature range provides a range or value that can be reduced by cooling. The temperature reduction can be measured as a result of flowing blood. Alternatively, the degree to which the electrical property (such as voltage or current) needs to increase to maintain a constant overtemperature or sensing temperature range can be measured and related to blood flow. Therefore, the overtemperature can be constant or can be a range that varies based on cooling.

[0013] In one embodiment, the present invention relates to a graphical user interface and a probe interface or processing system or display system or integrated cardiology display system (ICD) (each generally individually or collectively referred to as a "measurement system") that electronically communicates with a guidewire-based probe that simultaneously forwards pressure and flow data associated therewith. 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, Pressure and flow systems, and other intravascular pressure sensing or FFR determination devices and systems. In one embodiment, the measurement system and probe interface or the processing system and display system are a collection of the same device or multiple devices.

[0014] In one embodiment, the interface device receives signals representing flow and pressure at one or more locations along the blood vessel from a probe based on a guidewire. Before being introduced into the blood vessel, a probe sensor based on a guidewire is located in a catheter. In addition, before being introduced into the lumen of the blood vessel, the system obtains a zero flow reference value from inside the catheter. When calibrating a probe based on a guidewire, this zero flow reference can also be used as an input. During sensor calibration, atmospheric pressure can also be used as a zero point.

[0015] The timing of data collection and selection of a controlled environment (wherein data collection is performed) provides a zero point or origin relative to which other flow measurements and / or pressure measurements can be evaluated. The zero point or calibration point can be used with other parameters and transfer functions for transforming the guidewire-based probe signal data into flow data suitable for display and subsequent data analysis using one or more processors in the measurement system.

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

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

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

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

[0020] In part, the present invention relates to a method for collecting data related to a blood vessel. The method includes: storing guidewire-based probe data in one or more storage 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; using the guidewire-based probe data to determine a transfer function having a flow parameter as an output; using one or more of the first electrical signal and the second electrical signal to determine a blood pressure value for the blood vessel; using one or more of the first electrical signal and the second electrical signal to determine a blood temperature value for the blood vessel; using one or more of the first electrical signal and the second electrical signal and the transfer function to determine a blood flow value for the blood vessel; and displaying a pressure versus flow curve for the blood vessel. In one embodiment, the transfer function involves a flow parameter and an excitation voltage. In one embodiment, the transfer function involves a flow value and a temperature of one or more of the first resistor and the second resistor. In one embodiment, the method also includes identifying one or more of the occurrence of a maximum flow, a minimum flow, and a relative extreme of the flow and correlating such occurrences with intravascular or cardiac events.

[0021] In part, the present invention relates to an intravascular pressure and flow monitoring system. The system includes one or more storage devices; and a computing device in communication with the storage device, wherein the storage device includes instructions that can be executed 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 by a 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 by the guidewire-based probe and the interface device; and display a pressure-versus-flow curve generated based on the one or more intravascular pressure values ​​and the intravascular flow values, wherein the pressure-versus-flow curve changes over time.

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

[0023] In one embodiment, the one or more cardiovascular values ​​are selected from the group consisting of one or more indicators of flow rate, pressure value, maximum flow, minimum flow, relative extremes of flow, one or more blood flow reserve fraction (FFR) values, coronary blood flow reserve (CFR) value, coronary flow velocity reserve (CFVR) value, instantaneous blood flow reserve (IFR) value, and myocardial resistance (IMR) value.

[0024] In one embodiment, the system further comprises instructions for displaying one or more trajectories or signatures generated in response to intravascular probe data relative to one or more locations in the artery. In one embodiment, the system further comprises instructions for displaying a user interface comprising one or more indicators of flow rate, pressure value, maximum flow, minimum flow, relative extremes of flow, 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 myocardial resistance (IMR) values ​​generated using 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 function or other function in response to a second electrical signal from the measurement circuit formed by the guidewire-based probe and the interface device.

[0026] In part, the present invention relates to an intravascular pressure and flow monitoring adapter kit. The kit includes a power supply unit, the power supply unit including a first intravascular pressure measurement system output connection and a second intravascular pressure measurement system output connection, wherein the power output of the power supply unit ranges from greater than about 0.2 volts to less than about 12 volts, and the specifications of the power supply unit are adjusted to electrically connect to 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 ranges from about 0.3 volts to about 30 volts. In one embodiment of the kit, the kit further comprises a non-volatile storage medium comprising instructions that cause a computing device of the intravascular pressure monitoring system to: store a transfer function in a memory that outputs an intravascular flow value in response to an excitation voltage or temperature; and generate an intravascular flow value in response to a difference between (i) the excitation voltage or (ii) a fixed voltage and a voltage across a temperature-dependent resistor from the power supply unit and the transfer function.

[0028] In part, the present invention relates to a method of calibrating a flow monitoring device. The method includes: selecting an excitation voltage for a pressure sensor so that the temperature of the sensor and the temperature of blood in which the pressure sensor is disposed substantially match; determining the absolute temperature of blood in a vessel of interest; and measuring flow values ​​in the vessel using the pressure sensor. In one embodiment, the method includes: determining the absolute temperature of blood in the vessel of interest includes obtaining measurements during a change in a switch configuration in an interface system.

[0029] In part, the present invention relates to an integrated cardiology system. The system includes: a display system; a pressure and flow measurement system, the pressure and flow measurement system being in electrical communication with the display system; a processor, the processor being disposed within one of the display system or the pressure and flow measurement system; one or more panels generated using the processor and shown on the display, wherein the one or more panels include flow values ​​and pressure values ​​obtained using an intravascular probe, the intravascular probe including a pressure and flow sensor. In one embodiment, the one or more panels include a pressure versus flow curve, the pressure versus flow curve including one or more traces generated using intravascular pressure and flow data and also including an input for receiving a data signal from the intravascular probe, the intravascular probe including a temperature sensor for measuring temperature changes associated 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 changes based on stenosis due to contraction and other aortic or cardiac states, pressure changes in the aorta, and flow changes. In one embodiment, one or more panels include a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of measured values, a ratio of measured values ​​to derived values, a ratio of a first derived value to a second derived value, an area, one or more (FFR) values, 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 (IMR) values.

[0031] In part, the present invention relates to an intravascular pressure and flow monitoring system. The system includes: an intravascular pressure and flow interface system, which includes a wired interface or a wireless interface for receiving data from an intravascular probe; a display system, which is in electrical communication with the intravascular pressure and flow interface system; one or more storage devices, which include instructions for outputting a user interface on a display, the user interface including one or more panels with fields for one or more flow measurements; and a processor, which is in electrical communication with the intravascular pressure and flow interface system, the display system, and the one or more storage devices, the processor responsive to the instructions to cause the user interface to be output 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 into a flow rate using a transfer function. In one embodiment, the transfer function is in the form of a+b*lnx and / or a+b*x c In one embodiment, the display system outputs pressure measurements and flow rate measurements simultaneously. In one embodiment, the display system outputs pressure measurements and absolute temperature measurements simultaneously. In one embodiment, the display system displays one or more parameters or indicators corresponding to one or more signals obtained at the measurement location of the probe sensor.

[0033] In one embodiment, the one or more parameters or indicators are selected from the group consisting of a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of measured values, a ratio of measured values ​​and derived values, a ratio of a first derived value and a second derived value, an area, a (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 (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, wherein each current source is connected in series with one of the switches.

[0034] Coronary blood flow reserve-related features and implementation

[0035] In part, the present invention relates to methods and systems suitable for determining one or more coronary flow reserve (CFR) values ​​and fractional flow reserve (FFR) values, either individually or simultaneously, using a thermal convection device, such as an intravascular pressure and flow sensor and an intravascular data collection and processing system. Additionally, in part, the present invention also relates to determining CFR values ​​using an intravascular probe with a pressure sensor and constant temperature anemometer (CTA) or constant voltage excitation (CVEX) anemometer.

[0036] The present invention also relates to a method for determining coronary blood flow reserve data using an intravascular pressure or flow sensor. The method includes sampling an intravascular data collection probe to obtain one or more distal pressure values ​​(Pd) and one or more thermal convection data values ​​from a distal region of a blood vessel; 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 blood flow reserve fractions (FFR) values ​​from the one or more distal pressure values ​​and the one or more aortic pressure values; determining one or more coronary blood flow reserve (CFR) values ​​from the one or more thermal convection data values; and displaying one or more FFR values ​​and one or more CFR values ​​on a display unit.

[0037] 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 the temperature variable resistor of the thermal convection device, Q is the flow rate, and a and c are constants. In one embodiment, determining one or more coronary flow reserve (CFR) values ​​includes determining the temperature T measured at the hyperemic flow. hyp and the temperature T measured at the baseline flow bas In one embodiment, each CFR value is calculated using T hyp and T bas The form between , which is determined by a relationship that is an algebraic simplification of the inverse of the function, wherein b is a generalized base and c is a constant. In one embodiment, the FFR value and the CFR value are displayed as numerical values ​​and as a plotted graph that changes over time relative to a graphical user interface that includes one or more controls. In one embodiment, one of the one or more controls includes an enable CFR control that can be adjusted by a user to select between an FFR display mode and a combined FFR and CFR mode. In one embodiment, the method also includes tuning the temperature signal to find a maximum, minimum, or other level. In one embodiment, the tuning step is performed by adjusting the control until an audible or visual prompt indicating the tuning state appears.

[0038] In part, the present invention relates to a data collection method and / or a diagnostic method using the collected data (such as measured pressure values, temperature values, or flow values). The method includes setting a zero value for a distal pressure signal measured by an intravascular thermal convection device; positioning the intravascular thermal convection device to a delivery catheter opening; setting a zero value for a temperature signal measured by the intravascular thermal convection device before advancement into the vascular system; advancing the intravascular thermal convection device to a position distal to the catheter opening; making the intravascular thermal convection device pressure signal (Pd) equal to the aortic pressure (Pa) signal; tuning or optimizing the temperature signal of the intravascular thermal convection device when in a measurement position of interest; sampling the intravascular thermal convection device to obtain a baseline thermal convection signal value; sampling the intravascular thermal convection device to obtain a Pd value and a thermal convection device value for performing FFR and CFR calculations. In one embodiment, the method also includes verifying that the pressure equalization and flow signals return to baseline. In one embodiment, the method also includes displaying one or more FFR values ​​and one or more CFR values ​​relative to a graphical user interface, the graphical user interface including one or more axes and one or more control inputs. In one embodiment, the control input and user interface are implemented using a touch screen.

[0039] In part, the present invention relates to an intravascular data monitoring system. The system includes: an intravascular data collection system, which includes an interface for receiving data from an intravascular probe; a display system, which is in electrical communication with the intravascular data collection system; one or more storage devices, which include instructions for outputting a user interface on the display system, the user interface including one or more areas for displaying one or more CFR values ​​or plots thereof, the user interface including one or more areas for displaying one or more FFR values ​​or plots thereof; a processor, which is in electrical communication with the intravascular data collection system, the display system, and the one or more 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 determine one or more CFR values ​​and one or more FFR values ​​using the sampled Pa values, Pd values, and thermal convection data values.

[0040] In part, the present invention relates to a method for calibrating an intravascular data collection system. The method includes setting a baseline value for a distal pressure signal measured by an intravascular thermal convection device; positioning the intravascular thermal convection device to a delivery catheter opening; setting a baseline value for a temperature signal measured by the intravascular thermal convection device before advancement into the vascular system; advancing the intravascular thermal convection device to a position distal to the catheter opening; making the intravascular thermal convection device pressure signal (Pd) equal to the aortic pressure (Pa) signal; calibrating the temperature signal of the intravascular thermal convection device when in a measurement position of interest; and sampling the intravascular thermal convection device to obtain a Pd value and a thermal convection device value.

[0041] Stenosis Assessment and Flow Threshold / Peak-Guided Measurement Implementation

[0042] In part, the present invention relates to an intravascular pressure monitoring system and data collection device suitable for analyzing pressure drops in a non-congested state or a congested state, and identifying one or more flow thresholds and collecting or generating diagnostic data relative to data collected at such selected time points. In one embodiment, a pressure ratio (such as a distal to proximal ratio) or a pressure difference is collected over time at different one or more flow thresholds. The pressure and flow values ​​measured at each flow threshold can be used to calculate the arithmetic mean of the pressure ratio / pressure difference over multiple heartbeats.

[0043] In part, the present invention relates to a method for assessing a blood vessel. The method comprises: using one or more sensors to measure multiple intravascular blood flow values ​​and multiple blood pressure values ​​during one or more heartbeats; using one or more of the multiple intravascular blood flow values ​​to determine a flow threshold for one or more heartbeats; determining a proximal pressure value (Pa) and a distal pressure value (Pd) during the flow threshold; at the flow threshold for one or more heartbeats, calculating a first diagnostic parameter based on the Pa value and the Pd value; displaying the first diagnostic parameter for 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 multiple blood pressure values ​​include a relative proximal pressure value measured relative to stenosis and one or more of one or more aortic pressure values.

[0044] In one embodiment, the first diagnostic parameter and the second diagnostic parameter are selected from the group consisting of one or more indicators of Pa, Pd, Pd / Pa, Pa-Pd, flow rate, pressure value, maximum flow, minimum flow, relative extreme of flow, fractional flow reserve (FFR) value, coronary flow reserve (CFR) value, coronary flow velocity reserve (CFVR) value, instantaneous flow reserve (IFR) value, and myocardial resistance (IMR) value. In one embodiment, the flow threshold value is selected from the group consisting of the maximum flow during the cardiac cycle, the relative extreme flow value during the cardiac cycle, the portion of the maximum flow during the cardiac cycle, the maximum flow value of congestion, and the flow value of non-congestion.

[0045] In one embodiment, measuring multiple intravascular blood flow values ​​and multiple blood pressure values ​​also includes: measuring a first electrical signal associated with a first resistor and a second resistor arranged in the blood vessel; measuring a second electrical signal associated with the second resistor arranged in the blood vessel; using one or more of the first electrical signal and the second electrical signal to determine one or more of the blood pressure values ​​of multiple intravascular blood flow pressure values; using one or more of the first electrical signal and the second electrical signal to determine one or more blood temperature values ​​for the blood vessel; using one or more of the first electrical signal and the second electrical signal to determine the multiple intravascular blood flow values ​​for the blood vessel.

[0046] In one embodiment, one or more of the blood pressure values ​​is aortic pressure value or proximal pressure value. In one embodiment, the first diagnostic parameter is a plot of values ​​over time. In one embodiment, calculating the first diagnostic parameter includes calculating an average of a pressure ratio or a pressure difference for multiple cardiac cycles according to a flow threshold determined for each cardiac cycle. In one embodiment, the first diagnostic parameter is an average of a pressure ratio for multiple cardiac cycles or an average of a pressure difference for multiple cardiac cycles.

[0047] In part, the present invention relates to a method for assessing a blood vessel. The method includes: receiving intravascular blood flow data and blood pressure data obtained during one or more cardiac cycles, the intravascular blood flow data including a peak blood flow value; determining a flow threshold including the peak blood flow value; determining a first intravascular blood pressure (Pa) and a second intravascular blood pressure (Pd) at the peak blood flow for each heartbeat in one or more heartbeats; calculating one or more of the pressure difference between Pa and Pd for each of the one or more cardiac cycles and one or more of the pressure ratio Pd / Pa for each of the one or more cardiac cycles; and displaying diagnostic information about the blood vessel on a user display, wherein the diagnostic information includes one or more of the pressure ratio, the pressure difference, or a plot thereof. In one embodiment, calculating the pressure difference includes calculating an average of the pressure difference for multiple heartbeats.

[0048] In one embodiment, the method also includes receiving an electrical signal associated with a temperature change of an intravascular thermal convection device, wherein the intravascular thermal convection device is thermally connected to the blood vessel, wherein the temperature change is associated with a flow change during one or more cardiac cycles, and wherein the intravascular blood flow data includes the electrical signal; and determining a peak blood flow value from the electrical signal associated with the temperature change.

[0049] In one embodiment, the method also includes: receiving an electrical signal related to a temperature change of an intravascular thermal convection device, wherein the intravascular thermal convection device is thermally connected to the blood vessel, wherein the temperature change is related to a flow change during one or more cardiac cycles, and wherein the intravascular blood flow data includes the electrical signal; and determining a peak blood flow value from the electrical signal related to the temperature change.

[0050] Additional Implementations and Implementations

[0051] In part, the present invention relates to an intravascular pressure and flow monitoring system, the system comprising: one or more storage devices; and a computing device in communication with the storage device, wherein the storage device includes instructions that can be executed 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 by a 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 by the guidewire-based probe and the interface device; and display a pressure-versus-flow curve generated based on the one or more intravascular pressure values ​​and the intravascular flow values, wherein the pressure-versus-flow curve changes over time. In one embodiment, the pressure-versus-flow curve is displayed substantially in real time. In one embodiment, the transfer function T(x) is in the form of T(x)=a+b*ln(x), wherein x is the flow rate and a and b are constants. In one embodiment, the transfer function T(x) is in the form of T(x)=a+b*x c , where x is the flow rate, and a, b and c are constants.

[0052] In one embodiment, the system further comprises instructions for displaying one or more cardiovascular values ​​obtained during one or more time points. In one embodiment, the one or more cardiovascular values ​​are selected from the group consisting of one or more indicators of flow rate, pressure value, maximum flow, minimum flow, relative extremes of flow, 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 myocardial resistance (IMR) values.

[0053] In one embodiment, the system further comprises instructions for displaying one or more trajectories or signatures generated in response to intravascular probe data relative to one or more locations in the artery. In one embodiment, the system further comprises instructions for displaying a user interface comprising one or more indicators of flow rate, pressure value, maximum flow, minimum flow, relative extremes of flow, 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 myocardial resistance (IMR) values ​​generated using pressure and flow data from the intravascular probe.

[0054] In one embodiment, the system further includes instructions for determining one or more temperature values ​​using a linear function or other function in response to a second electrical signal from the measurement circuit formed by 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 a pressure sensor so that the temperature of the sensor and the temperature of the blood in which the pressure sensor is disposed substantially match; determining the absolute temperature of the blood in a vessel of interest; and measuring a flow value in the vessel using the pressure sensor. In one embodiment, determining the absolute temperature of the blood in the vessel of interest includes obtaining measurements during a change in a switch configuration in the interface system.

[0055] In one embodiment, the intravascular pressure and flow monitoring system also includes: a display system; a pressure and flow measurement system, which is in electrical communication with the display system and includes the computing device; the computing device is arranged in one of the display system or the pressure and flow measurement system; and one or more panels generated using the computing device and displayed on the display, wherein the one or more panels include flow values ​​and pressure values ​​obtained using an intravascular probe, and the intravascular probe includes a pressure and flow sensor.

[0056] In one embodiment, one or more panels include a pressure versus flow curve, the curve including one or more traces generated using intravascular pressure and flow data and also including an input for receiving a data signal from the intravascular probe, the intravascular probe including a temperature sensor for measuring temperature changes associated with flow values. In one embodiment, one or more panels include a signature, a trace, a slope, a maximum point, a minimum point, a ratio of measured values, a ratio of measured values ​​and derived values, a ratio of a first derived value and a second derived value, an area, one or more (FFR) values, 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 (IMR) values.

[0057] In one embodiment, the intravascular pressure and flow monitoring system further includes instructions for processing coronary flow reserve data using an intravascular pressure or flow sensor, the processing comprising: sampling an intravascular data collection probe to obtain one or more distal pressure values ​​(Pd) and one or more thermal convection data values ​​from a distal region of the blood vessel; 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 flow reserve fractions (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 one or more FFR values ​​and one or more CFR values ​​on a display unit, wherein each CFR value is determined using a transfer function. In one embodiment, the transfer function is in the form of T=a+c*lnQ, wherein 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. In one embodiment, each CFR value is determined using T hyp and T bas The form between The form is determined by the relationship of, which is an algebraic simplification of the inverse of the function of claim 3, wherein b is the generalized base and c is a constant.

[0058] In part, the present invention relates to a method for intravascular pressure and flow monitoring. The method comprises: using one or more sensors to measure multiple intravascular blood flow values ​​and multiple blood pressure values ​​during one or more heartbeats; using one or more of the multiple intravascular blood flow values ​​to determine a flow threshold for one or more heartbeats; determining a proximal pressure value (Pa) and a distal pressure value (Pd) during the flow threshold; at the flow threshold for one or more heartbeats, calculating a first diagnostic parameter based on the Pa value and the Pd value; and displaying the first diagnostic parameter for 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 can be a pressure difference Pa-Pd or a pressure ratio Pd / Pa. In one embodiment, the multiple blood pressure values ​​include one or more of a relative proximal pressure value measured relative to stenosis and one or more of one or more aortic pressure values.

[0059] In one embodiment, the first diagnostic parameter and the second diagnostic parameter are selected from the group consisting of one or more indicators of Pa, Pd, Pd / Pa, Pa-Pd, flow rate, pressure value, maximum flow, minimum flow, relative extreme of flow, fractional flow reserve (FFR) value, coronary flow reserve (CFR) value, coronary flow velocity reserve (CFVR) value, instantaneous flow reserve (IFR) value, and myocardial resistance (IMR) value. In one embodiment, the flow threshold value is selected from the group consisting of the maximum flow during the cardiac cycle, the relative extreme flow value during the cardiac cycle, the portion of the maximum flow during the cardiac cycle, the maximum flow value of congestion, and the flow value of non-congestion. In one embodiment, measuring multiple intravascular blood flow values ​​and multiple blood pressure values ​​also includes: measuring a first electrical signal associated with a first resistor and a second resistor arranged in the blood vessel; measuring a second electrical signal associated with the second resistor arranged in the blood vessel; using one or more of the first electrical signal and the second electrical signal to determine one or more of the blood pressure values ​​of the multiple intravascular blood flow pressure values; using one or more of the first electrical signal and the second electrical signal to determine one or more blood temperature values ​​for the blood vessel; and using one or more of the first electrical signal and the second electrical signal to determine the multiple intravascular blood flow values ​​for the blood vessel.

[0060] In one embodiment, calculating the first diagnostic parameter includes calculating an average value of a pressure ratio or a pressure difference for multiple cardiac cycles according to a flow threshold value determined for each cardiac cycle. In one embodiment, the first diagnostic parameter is an average value of a pressure ratio for multiple cardiac cycles or an average value of a pressure difference for multiple cardiac cycles. In one embodiment, the method includes: receiving an electrical signal related to a temperature change of an intravascular thermal convection device, the intravascular thermal convection device being thermally connected to the blood vessel, the temperature change being related to a flow change during 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 related to the temperature change.

[0061] In one embodiment, the method also includes the step of calibrating the intravascular data collection system, the steps comprising: setting a baseline value for a distal pressure signal measured by an intravascular thermal convection device; positioning the intravascular thermal convection device to a delivery catheter opening; setting a baseline value for a temperature signal measured by the intravascular thermal convection device before advancing into the vascular system; advancing the intravascular thermal convection device to a position distal to the catheter opening; making the intravascular thermal convection device pressure signal (Pd) equal to the aortic pressure (Pa) signal; calibrating the temperature signal of the intravascular thermal convection device when at a measurement position of interest; and sampling the intravascular thermal convection device to obtain a Pd value and a thermal convection device value. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] The drawings are not necessarily to scale, emphasis instead generally being placed upon the exemplary principles. The drawings are to be regarded in all respects as illustrative and not intended to be limiting of the invention, the scope of which is defined solely by the claims.

[0063] Figure 1A 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.

[0064] Figure 1B 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.

[0065] Figure 2A is a schematic diagram of a blood vessel having a guidewire-based probe therein for sensing pressure and flow according to an exemplary embodiment of the present invention.

[0066] Figure 2B Schematic diagram of a sensing region and its associated components of an exemplary guidewire-based probe embodiment suitable for simultaneously measuring pressure and flow according to an exemplary embodiment of the present invention.

[0067] Figure 2C 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 invention.

[0068] Figure 2D is a perspective view of a guidewire-based probe showing an encapsulator surrounding a sensor array according to an exemplary embodiment of the present invention.

[0069] Figure 3 is a circuit diagram including various resistors and nodes representing components of a probe, connectors, and contact pads associated therewith according to an exemplary embodiment of the present invention.

[0070] Figure 4A is a circuit diagram including various resistors and nodes representing components of an intravascular probe and an interface or processing system in a bridge configuration according to an exemplary embodiment of the present invention.

[0071] Figure 4B is a circuit diagram including various resistors and nodes representing components of an intravascular probe and an interface or processing system in a bridge configuration according to an exemplary embodiment of the present invention.

[0072] Figure 5A For use with Figure 4A Schematic diagram of a signal sampling system used with an intravascular probe in conjunction with a measuring bridge.

[0073] Figure 5B Schematic diagram of a control system for a constant temperature angiometry (CTA) embodiment using a guidewire-based probe according to an exemplary embodiment of the present invention.

[0074] Figure 5C FIG. 1 is a schematic diagram of a thermostatic control system for monitoring excitation voltage changes according to an exemplary embodiment of the present invention.

[0075] Figure 5D FIG. 4 is a schematic diagram of a flow rate calculation system implemented using a constant excitation voltage (CVEX) according to an exemplary embodiment of the present invention.

[0076] Figure 5E is a schematic diagram of a software signal processing diagram for simultaneously measuring pressure and flow using CVEX according to an exemplary embodiment of the present invention.

[0077] Fig. 6A and Figure 6B A plot and representation of transfer functions, respectively, for a CTA implementation and a CVEX implementation for monitoring pressure and flow using an intravascular probe according to an exemplary embodiment of the present invention.

[0078] Fig. 7A A flow signal measured using an embodiment of the present invention (blue) is shown compared to a baseline flow signal (red). The measurement is performed using a blood flow model.

[0079] Figure 7B Plot showing flow velocity pullback from distal LAD to proximal LAD. The recording was performed in a single beating porcine heart.

[0080] Fig. 8A Shown is a plot of pressure and flow versus time obtained using a pressure and flow sensing probe with the sensor placed in the proximal RCA in a porcine heart according to an exemplary embodiment of the present invention.

[0081] Figure 8B Shown is a plot of pressure and flow versus time obtained using a pressure and flow sensing probe with the sensor placed in the proximal LAD in a porcine heart in accordance with an exemplary embodiment of the present invention.

[0082] Figure 8C A plot of pressure versus flow with a loop or trace obtained for RCA is shown using a pressure and flow sensing probe according to an exemplary embodiment of the present invention. Fig.8D The corresponding points of the marks are shown in .

[0083] Fig.8DA plot of pressure and flow versus time showing a flow velocity profile obtained for an RCA using a pressure and flow sensing probe according to an exemplary embodiment of the present invention. Figure 8C The corresponding points of the marks are shown in .

[0084] Fig. 8E A plot of pressure versus flow with a loop or trajectory obtained for LCA using a pressure and flow sensing probe according to an exemplary embodiment of the present invention is shown. Fig.8F The corresponding points of the marks are shown in .

[0085] Fig.8F A plot of pressure and flow rate versus time for a flow velocity profile obtained by LCA according to an exemplary embodiment of the present invention is shown. Fig. 8E The corresponding points of the marks are shown in .

[0086] Fig.9A Shown is a plot of pressure and flow versus time in the proximal left anterior descending coronary artery according to an exemplary embodiment of the present invention.

[0087] Fig. 9B A plot of myocardial resistance versus time is shown according to an exemplary embodiment of the present invention. Fig. 9B The plot is divided by Fig.9A The pressure and flow signals are derived from the

[0088] Fig. 10A and Fig. 10B The example embodiment of the present invention is shown for a normal scene ( Fig. 10A ) and abnormal scenarios ( Fig. 10B ) is a plot of pressure versus flow (top) and a plot of pressure versus time (bottom). Fig. 10B The abnormal scenario shown in was created using an occlusive balloon causing a myocardial infarction.

[0089] Fig.11 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 invention.

[0090] Fig. 12A Flowchart of an exemplary method of intravascular data analysis and display according to an exemplary embodiment of the present invention.

[0091] Fig. 12B Flowchart of an exemplary method of intravascular data analysis and display according to an exemplary embodiment of the present invention.

[0092] FIG. 13A to FIG. 13D 2 is a screen shot of an exemplary user interface and data display during viewing mode according to an exemplary embodiment of the present invention.

[0093] Fig.14 is a graph illustrating the performance of a system according to an exemplary embodiment of the present invention for determining a CFR value compared to a reference CFR value.

[0094] FIG. 15A to FIG. 15D 2 are screen shots of exemplary user interfaces and data displays according to exemplary embodiments of the present invention.

[0095] Fig.16 A diagnostic method for flow rate threshold detection according to an exemplary embodiment of the present invention is provided.

[0096] Fig.17A and Fig. 17B 1 is a flow chart illustrating an embodiment of a method for collecting, analyzing, and displaying intravascular data regarding diagnostic information of interest according to an exemplary embodiment of the present invention.

[0097] Fig.18 Plots of pressure ratios and pressure differences versus pressure measurements (top) and flow measurements / measurements related to flow values ​​(bottom) obtained at multiple flow thresholds obtained at different points in time using a sensing device according to an exemplary embodiment of the present invention. DETAILED DESCRIPTION

[0098] Various data collection and analysis systems can be used to obtain information about the coronary system. Data obtained from a vessel using a device or derived from intravascular or extravascular measurements associated therewith can be analyzed or displayed to provide correlations and inferences to assist researchers and clinicians. For example, various measurement systems and intravascular probes can be used to determine the blood flow reserve fraction (FFR) about a vessel using a pressure sensor-based device. Intravascular ultrasound (IVUS) is an imaging mode that uses sound waves to image multiple portions of a vessel. In turn, optical coherence tomography (OCT) is an imaging mode that uses an interferometer to obtain distance measurements relative to a vessel or an object placed therein.

[0099] Intravascular data collection devices can be used to generate and receive signals including diagnostic information about the blood vessels using the above devices. These devices can include, but are not limited to, imaging devices (such as optical or ultrasound probes), pressure sensor devices, flow sensors, temperature sensors, ion and other chemical sensors, and other devices suitable for collecting data about blood vessels or other components of the cardiovascular system. Angiography systems 95 and other external sensors 97 in the catheterization laboratory can also be used to image the patient and transmit the data along with other devices and systems 10, 20 described in the text (such as, for example, in Figure 1A and Figure 1B The data in the measurement system is provided.

[0100] Using such devices and systems, values ​​for coronary flow reserve (CFR) and fractional flow reserve (FFR) may be determined, either individually or simultaneously, as described in more detail herein. In addition, pressure ratios and pressure differences may be selectively measured at one or more specific time points. These points may correspond to flow thresholds, such as peak flow at points in the cardiac cycle that correspond to periodic events, or other flow extremes, or values ​​related to or derived from flow values. An example of such a periodic event is a point of peak or maximum flow that occurs repeatedly as the heart expands and contracts, although not necessarily at the same level of flow.

[0101] In part, the present invention relates to a plurality of methods, systems and devices by which intravascular blood flow measurements and pressure measurements can be obtained and these measurements can be used to generate diagnostic feedback for patients. As used herein, reference to obtaining blood flow measurements, measuring blood flow values ​​or parameters, and similarly reference to blood flow refers to flow velocity values ​​or related values ​​rather than absolute flow values. Specifically, various embodiments of the disclosure described herein simultaneously perform intravascular pressure measurements and simultaneously obtain blood flow information or parameters related to such flows. Methods based on CTA and CVEX velocity measurement techniques can be used in one or more embodiments to perform simultaneous flow and pressure measurements on a blood vessel using a single guidewire-based probe comprising one or more optical or electrical sensors. The probe may include other sensors, such as OCT, IjUS, and other data collection sensors.

[0102] In a CTA implementation, a constant temperature is maintained for the temperature sensor. A control system is used to maintain the temperature and can detect when a change in voltage required to maintain the temperature occurs. Thus, the cooling effect of the fluid flowing relative to the temperature sensor can be converted into a time-varying voltage corresponding to a flow parameter. In contrast, for a CVEX implementation, the excitation voltage of the temperature sensor is held constant, and changes in resistance, impedance, and other parameters that vary with voltage, current, or time can be measured to represent a flow parameter.

[0103] Intravascular blood flow measurements can be used alone or in combination with other measurements to display diagnostic information of interest on a real-time or near real-time basis over a time period greater than about 0 seconds to about 5 seconds. Various types of data about a patient obtained using intravascular probes and other catheterization laboratory measurement equipment (such as angiographic system and room temperature, oximetry, etc.) can be integrated and displayed using an integrated cardiology display system (ICD), which can include one or more measurement systems. Additional details about these features are described herein.

[0104] Figure 1A and Figure 1BSystems 10, 20 are shown, suitable for use with different types of guidewire-based devices in a catheterization laboratory or other environment, with which intravascular blood flow measurements can be obtained and displayed. Figure 1A In FIG. 8 , an intravascular probe 20 is shown that includes a wired connection 90 to an interface system 80 . In contrast, in FIG. Figure 1B In FIG, an intravascular probe 35 is shown, which includes a wireless connection 91 to the interface system 82. Figure 1A and Figure 1B Each device shown in comprises guide wire 40 and one or more sensors placed at the distal end of guide wire, and these sensors constitute the parts of intravascular probe. The size of the distal end of guide wire is set to be inserted into a blood vessel (such as a coronary artery). One or more sensors define a sensing area, and the sensing area is suitable for sensing or measuring one or more of pressure value P, flow value Q, value related to flow, temperature value T, and changes in any of the foregoing. PQT sensing area 45 can correspond to the end of intravascular probe. Pressure sensor can be electrical, mechanical, or optical suitable for a given implementation.

[0105] Figure 1A and Figure 1B Also shown are enlarged views of the probe ends of each corresponding type of intravascular probe. As shown in the enlarged view, the guide wire 40 is adjacent to the outer cover or encapsulator 50 or other supporting structure that defines the cavity above the sensor array 43. In one embodiment, the outer cover or encapsulator can be a metal tube. 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, such as an optical fiber-based pressure sensor. The sensor array may include optical flow sensors, mechanical flow sensors, and other flow sensors. Electrical connections or optical connections (depending on the type of pressure and flow sensors) extend from the sensor array to the proximal connector via the guide wire. The probe end may include one or more coils 55, such as for navigational or angiographic detection, such as Figure 2D shown.

[0106] like Figure 1A and Figure 1B As shown, the proximal connectors 70 , 72 distinguish between the two types of probes 30 , 35 . Figure 1A The proximal connector 70 communicates with the probe tip at the distal end and is connected to the guide wire at the proximal end of the probe. Figure 1A The proximal connector 70 is shown connected to the probe interface / processing system 80 via a releasable wired connection 90. In contrast, Figure 1B The intravascular probe 35 has a guidewire terminating in a proximal connector 72 that includes a transmitter 75 .

[0107] about Figure 1B In a wireless embodiment, the transmitter wirelessly transmits the signal from the probe to the probe interface / processing system 82, and Figure 1A The embodiment uses a wired connection 90. In one embodiment, the proximal connector and the transmitter also include a power source, such as a battery. The proximal connectors each include an electrical connection or an optical connection to a sensor array disposed in the probe end. The proximal connector may also include an interface circuit that forms a wired or wireless bridge to a measurement system, such as a probe interface / processing system.

[0108] In one embodiment, in a wired connector based system (which uses an electric pressure sensor), the interface electronics (such as Figure 4A The interface electronics in the display system 87 are located within another measurement system. The display system, interface / processing system, and other systems having an input for receiving an intravascular probe signal can be separate systems or combined to varying degrees into one or more systems, such as an ICD. Analog-to-digital conversion, signal processing and conversion of raw signal data to calibration data, and a graphical user interface for real-time presentation of pressure, flow, and temperature data can be implemented in one or more of the systems described herein that directly or indirectly receive probe signals or data, including data generated from probe signals or data received from a given intravascular probe.

[0109] The interface or interface unit is 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 probe based on the guide wire into flow data and pressure data. The time-varying electrical signals can be current, voltage, resistance change, temperature change, or other data related to the flow or pressure in the blood vessel. The interface and display are formatted and programmed to display one or more panels. The panel can include multiple parts of the display, such as the parts used in the measurement system for pressure data, ultrasound images, angiography images, OCT images, and other intravascular images and data. A display system or other measurement system can be used to control one or more such panels (such as D1, D2 and D3) and program them to display flow data as real-time curves in the time domain. Pressure data can be displayed simultaneously with flow data. FFR values ​​based on pressure data can also be displayed. Various tracks and loops as described herein can also be displayed together with points of interest.

[0110] The display system includes various panels, displays or GUIs, such as D1, D2 and D3. These panels can represent 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 can show a curve of pressure versus flow and real-time FFR data obtained using pressure measurement or other measurement. D1, D2 or D3 can also show other intravascular data of interest, including imaging data, relative extremes, maximum flow, minimum flow, maximum pressure, minimum pressure, myocardial resistance, flow data, stent implantation images, and other details of interest.

[0111] In one embodiment, flow data is displayed in the same manner as pressure data or in a compatible or synchronized format. For example, an additional panel (such as D1 or D2 or D3) can be added to an existing user interface or data display screen for a measurement system, such as an FFR system or a combined or multi-mode intravascular data collection system. One or more additional panels can simultaneously display pressure and flow information, such as by means of pressure and flow curves or by other representations integrated with FFR results. The display or interface can be in electrical communication (such as by wireless communication) with an interface unit for a guidewire-based probe, OCT, FFR, IVUS, or other intravascular data collection system or a part of the electrical communication. In one embodiment, a transfer function or calibration function is used to calibrate a guidewire-based probe and use parameters stored in a memory as input, which is a part of a calibration system 93. In one embodiment, the calibration system 93 can be a part of a control system 92.

[0112] D1, D2 and D3 can provide a control user interface for the flow and pressure measurement system. In addition, information or graphical user interface panels D1, D2, D3, etc. can be used to display 7A to 10B . Although D1, D2, and D3 are shown, these are provided as examples and not limitations. Thus, various additional or fewer displays, panels, or sub-panels may be used for one or more of the real-time type storage data and user interfaces described herein.

[0113] In a system based on a wireless probe, in one embodiment, the interface electronics are located inside the proximal connector and the transmitter. In one embodiment, analog-to-digital conversion of signal data obtained about the blood flowing in the blood vessel is performed in the proximal connector. In addition, the conversion of raw data to calibration data can be performed by circuit elements or processors in the proximal connector and the transmitter or in the display system. In one embodiment, a graphical user interface (GUI) for real-time presentation of pressure, flow, and temperature data is implemented in the display system.

[0114] In part, embodiments of the present invention relate to various features of pressure sensing devices, measurement systems, and software associated therewith suitable for pressure monitoring and flow monitoring. Pressure monitoring and flow monitoring can be performed using a guidewire-based probe and a semiconductor device that includes a component that undergoes electrical changes in response to flow and pressure changes. Simultaneous pressure and flow measurement is desirable for a large number of clinical measurements, such as coronary flow reserve (CFR), coronary flow velocity reserve (CFVR), flow reserve fraction (FFR), and myocardial resistance index (IMR). In one embodiment, the maximum flow value or other flow values ​​of interest (such as the area from the PQ plot) are identified using one of the embodiments described herein so that one or more of CFR, CFVR, FFR, or IMR can be performed in response to such values. The embodiments described herein use a guidewire-based probe of a measurement system and associated software and electrical components to support methods for performing these processes and measurements.

[0115] The probe based on the guide wire can be used together with the measurement platform and the software-based method described in this article to measure pressure and flow simultaneously based on electrical signal changes. These components provide useful diagnostic tools and various interface types for real-time display of data. According to the ability to obtain such data from the electrical signal from the probe based on the guide wire, pressure and flow data can be displayed when the probe is in the patient. Conversely, pressure and flow data can be drawn together in real time into pressure contrast flow or PQ plotting diagram and for triggering events or as a diagnostic tool as described in this article. Stents can be deployed to the position identified by angiography system or other imaging systems along the guide wire of the probe or using the silk or device of other deployable catheters, which is registered with the position of the pressure and flow probe in the patient and its output data.

[0116] like Figure 2A As shown, a blood vessel 100 is shown, which can be, for example, a segment of a coronary artery. Blood flows in the blood vessel 100 and throughout the rest of the artery, and experiences flow changes and pressure drops when the blood encounters a constriction (such as a stenosis) area 120 in the flow path, as shown. The wall 150 of the blood vessel 100 surrounds the lumen 200 through which the blood flows. A pressure sensor-based device 250 (such as a guidewire-based probe) can be inserted into the lumen 200 of the blood vessel 100 to obtain data about the blood vessel 100. The sensing area 300 of the device 250 (in which flow and pressure sensing is performed) is exposed to the blood, but can be surrounded by an encapsulator, cover or other structural support or other structure. The encapsulator, cover or other elongated support area or member provides structural support while allowing an opening for the sensing area.

[0117] A guidewire 320 including an electrical lead in communication with circuit elements in region 300 may be used to introduce device 250 into lumen 200 of a blood vessel, such as Figure 2A As shown. In one embodiment, the guidewire 320 is part of a guidewire-based probe. Typically, the pressure sensor-based device 250 is placed in a catheter (not shown). Measurements can be obtained in the catheter during which the flow is constrained or nearly zero to provide a baseline or calibration value for the flow. In one embodiment, the guidewire can terminate at a wireless proximal connector PC.

[0118] In one embodiment, the electric lead arranged in the guide wire and the probe based on the guide wire terminate in a connector or wireless device, so that data can be forwarded to a probe interface system 340 (also referred to as an interface unit). The probe interface system or unit 340 can perform measurement calculations based on the signal from the probe. Alternatively, the system 340 can receive signals, and these signal encodings use the results of the calculations performed by the circuit or processing element arranged in the probe (such as, for example, arranged in the proximal connector of the probe). In one embodiment, the interface unit 340 is a component or a subsystem of a measurement unit. In one embodiment, the interface unit 340 communicates with a measurement system 390, which may include a display unit or an ICD. System 340 and system 390 may include a power supply and other adapter components as described herein, to provide or control overtemperature or excitation voltage. The adapter component may be used to improve an existing pressure monitoring system.

[0119] Measurement or interface unit 340 can include circuit elements, and these circuit elements are selected to be balanced or operated with the circuit elements arranged in the probe based on the guide wire. The interface unit can also include software, control system and data analysis and display equipment and processor suitable for pressure, flow and relative extreme values ​​of pressure and flow being graphically displayed. In one embodiment, the control system is programmed to trigger pressure measurement, flow measurement or perform FFR, CFR, CFVR or other processes or calculations when one of the following occurs: maximum flow, maximum pressure, relative maximum flow, relative maximum pressure and other values ​​or threshold values.

[0120] Figure 2B Shows about Figure 2AAdditional details of the sensing area 300 of the guidewire-based probe. The guidewire 320 generally includes a sensing area 300, which can be partially covered or otherwise supported by an encapsulator exposed to flowing blood. The sensing area can be cooled directly or indirectly by the flowing blood. The temperature of the sensing area can be increased to be equal to or greater than the temperature of the flowing blood. Without being limited to a specific mechanism, in one embodiment, the flowing blood contacts the sensing area 300 and transfers heat therefrom. In another embodiment, the flowing blood transfers heat from the encapsulator and other parts of the guidewire or other supporting structures, which are arranged around the sensing area 300 and are thermally connected to the sensing area 300. Therefore, the sensing area, encapsulator, and surrounding materials can be sized and made of suitable thermally conductive materials to increase heat transfer, thereby improving the detection of blood flow parameters.

[0121] In one embodiment, if Figure 2B As shown, the sensing area 300 of the probe based on the guidewire is in fluid communication with the surrounding blood. The sensing area is limited by an encapsulator or other barrier arranged around the sensing area. In one embodiment, the sensing area is directly cooled by the flowing blood. In another embodiment, the heat transfer through the encapsulator or other components of the probe supporting the sensing area is related to one or more blood flow parameters. Efficient heat transfer to the sensing area (whether or not in direct contact with the surrounding blood) improves the accuracy of thermal response and flow measurement. In one embodiment, the encapsulator does not exist.

[0122] In one embodiment, a piezoelectric film 350 is disposed on a semiconductor substrate 400. The film 350 moves in response to changes in pressure and acts as an active resistor or RA. In turn, a reference resistor (which is also referred to as a passive resistor RP) is also disposed or formed on the semiconductor substrate 400. In various configurations for different probe embodiments, the pressure sensor and the reference or passive resistor can be electrically connected to one or more electrical leads or other electrical components.

[0123] For example, electrical leads L1 and L2 are shown in electrical communication with resistors RP and RA, respectively. Figure 2C The semiconductor chip portion 128 of the wire-based probe device is shown, which includes a semiconductor substrate and an active resistor RA and a passive resistor RP. In one embodiment, one or more electrical leads (such as lead L1 and lead L2) are connected to the measurement system 340 through a connector or the end of the wire, and the electrical leads are integrated as part of the wire-based probe. The connection to the ground terminal can also be another connection from the wire-based probe, such as Figure 2B As shown. The pressure sensor can also be implemented using an optical sensor (such as a fiber-optic based calibrator). The optical sensor can be integrated with other hot wire anemometer equipment.

[0124] Temperature, pressure, and flow data collection

[0125] Pressure sensor-based devices include a miniature pressure sensor mounted in the tip of a guidewire as discussed herein. The pressure sensor is typically placed in a Figure 2B and Figure 2C The pressure sensor is part of a sensor array connected to the guide wire and is formed in part by a semiconductor substrate such as the one shown in FIG. Figure 1A and Figure 1B In one embodiment, the sensor array includes a sensor adapted to perform flow measurement, pressure measurement, or both. Figure 2D An exemplary representation of a sensing device, such as an intravascular probe 220 having an encapsulator 50 and a sensor array 43, is shown in FIG. The guidewire-based probe 220 may include two or more measuring resistors, such as, for example, RA and RP as part of the sensor array. The pressure sensor has a thin film with a tensile strength resistor in communication with the thin film, such as Figure 2C As the pressure changes, it affects the sensor film and in turn changes the resistance in the tensile strength resistor (also called active resistor RA).

[0126] RA is typically sensitive to temperature. A similar reference resistor or passive resistor RP is placed on substrate 400, which is only sensitive to temperature. The reference resistor facilitates compensation for temperature changes that can change the pressure signal or act as noise. Therefore, in one embodiment, one wire-based probe resistor is sensitive to pressure and temperature (RA) and the other wire-based probe resistor is only sensitive to temperature (RP).

[0127] The resistor is connected to measurement electronics which can be placed inside the interface unit or measurement system or which communicates electrically with the interface unit or measurement system via a micro cable. The selected cable is sized to fit over the guide wire. Since the cable is very thin, the resistor is a 、r p and r g Has significant resistance values, typically between about 40 ohms and about 70 ohms, depending on length. Micro cables are also temperature sensitive. Figure 3 The electrical equivalent model is shown in FIG. The sensor array is connected to an elongated guidewire shown in schematic form, which terminates at a proximal connector. Figure 1A and Figure 1B As shown, the proximal connector may include a transmitter in a wireless implementation, or use a wired connection for data signal transmission as an alternative implementation.

[0128] Guidewire-based probe enclosure and flow directing components

[0129] Figure 2D A guidewire-based probe (such as in Figure 1A , Figure 1B , Figure 2A , Figure 2B and Figure 2C The end 220 of the guidewire-based probe (shown in FIG. 1 ) is exposed through an opening in the encapsulator 50. The encapsulator or cover (which may be a tube with openings on its sides) is adjacent to the guidewire portion as shown and defines an opening through which one or more components of the sensor array are visible. The role of the encapsulator is to provide structural support for the guidewire-based probe while allowing the flow of blood to pass relative to the sensing area and maintain contact and cooling the end of the probe. In one embodiment, in response to thinning or removal of the encapsulator, V TOFFS -V P The sensitivity of the signal is increased. Thus, a combined pressure and flow measurement probe can be used with or without an encapsulator.

[0130] Electrical interface components

[0131] When a guidewire-based probe including RA and RP is used to measure pressure and flow, the probe sends the data to an interface or display system such as, for example, a RadiAnalyzer, RadiAnalyzer Xpress, Quantien, or Aeris system. Figure 3 A guidewire-based probe device (with its own circuit element arrangement) is shown in FIG. Figure 4A The electronics of the measuring system shown form a bridge when connected, such as, for example, a Wheatstone bridge.

[0132] like Figure 3 As shown in the circuit diagram, R A and R P represents a resistor on the semiconductor substrate 400, and r a 、r g and r p Corresponds to the microcable, including the tie and connector of a given guidewire-based probe. The resistance of the ground cable is r g . Active resistor R A and passive resistor R P The range of R can be from about 2200 ohms to about 3200 ohms, with a typical value of 2700 ohms. AThe pressure sensitivity of is at least about 7.9 ppm / mmHg, and typically about 10 ppm / mmHg. Therefore, for a typical guidewire-based probe sensor, the ratio of resistance to pressure sensitivity is about 2700*10 / 1000000=27 mQ / mmHg. A and R P The temperature sensitivity of the active resistor R is at least 400ppm / °C, and typically 500ppm / °C. This means that for a typical sensor, the ratio of resistance to temperature is about 2700*500 / 1000000 = about 1.35Ω / °C. A change of 0.02°C corresponds to a change in the active resistor R A 1mmHg change.

[0133] Figure 4A The electronic components of the interface or measurement system connected to the electronic components of the guidewire-based probe are shown. The active resistor and the a The active resistor connection cable of the probe is connected to the interface or measurement system node A. In turn, when the guidewire-based probe is connected to the measurement device, node A is in electronic communication with resistor R1. In one embodiment, V is measured from node A. A Passive resistors and resistors with resistance r p The passive resistor connection of the probe engages with the node P of the interface or measurement system. In turn, when the guidewire-based probe is connected to the measurement device, node P engages with the resistor R 2 Electronic communication. In one embodiment, V is measured from node P. P .

[0134] With resistance r g The ground cable is connected to the ground terminal G. The excitation voltage V EXC is applied to resistor R1 and resistor R2. Resistor R1 and resistor R2 are arranged in one or more systems (such as a probe interface system). In one embodiment, V EXC is the Wheatstone bridge excitation voltage. In one embodiment, the bridge excitation voltage ranges from about 1 volt to about 15 volts. In one embodiment, R1 and R2 can range from about 2000 ohms to about 3000 ohms. In one embodiment, the Wheatstone bridge is used by the guidewire-based probe interface using the excitation voltage V EXC to stimulate, and measure V A and V P The potential difference between V TOFFS and V P The temperature is measured between 10%. The 10% constraint is chosen so that P OFFS Can level the bridge. V TOFFS The voltage corresponds to a voltage substantially equal to V at about 37°C. P The bias voltage.

[0135] Still refer to Figure 4A , V POFFS voltage (which is applied positively and negatively as V POFFS+ and V POFFS- ,like Figure 4A ) corresponds to the bias voltage used to level or balance the nodes A and P on the Wheatstone bridge. POFFS is the bias voltage used to balance the pressure channel to compensate for the resistance difference between RA and RP. Assuming a temperature of about 37°C and zero pressure at normal atmospheric pressure (760 mmHg), V POFFS is adjusted to the VA and V P Zero potential is achieved between them.

[0136] like Figure 4A As shown, connection of the respective electrical components of the guidewire-based probe and the measurement system allows the excitation voltage to be applied in a bridge configuration or to allow other current levels or voltage levels to be maintained as required to support CTA- or CVEX-based methods. Figure 5A Shows how to use DSP to sample, convert and process Figure 4A The voltage of the measurement bridge in the circuit can be amplified using a programmable gain before analog-to-digital conversion. A and V P .

[0137] When connecting a guidewire-based probe to a RadiAnalyzer, Xpress, Quantien, or Pressure and flow systems, such as Figure 1B The wireless interface system shown has an electrical signal interface or an equivalent or similar interface that forms a measurement bridge with the transmitter of the wireless intravascular probe. The guidewire-based probe interface unit or measurement system includes interface electronics that sample the analog signal of the bridge (such as a Wheatstone bridge or other balanced circuit device). Figure 4B An example of such interface electronics is shown in .

[0138] Specifically, Figure 4B FIG. 1 is a circuit diagram showing interface electronics suitable for use with a wireless intravascular flow and pressure sensor. The dashed area corresponds to electrical components in an intravascular probe. For example, Figure 1B The implementation method can be Figure 4BThe right side of the figure shows how the electronic components of the guidewire-based probe are connected to the constant current interface circuit. The constant current source can be switched into contact with the circuit using switches S1, S2, S3, and S4. These switches can be physical switches, multiplexers, or software controls implemented as current sources. Resistors R1 and R2 are fixed precision resistors. In one embodiment, one or more current sources I are arranged in the proximal connector. In one embodiment, V TOFFS The voltage is basically equal to V P By measuring the voltage difference V A -V P , the pressure measurement can be derived. TOFFS -V P Voltage derived temperature. Constant current circuits use anemometer methods (such as CVEX, CTA, etc.) to create current-induced heating of the wire-based probe chip, which is sufficient for flow measurement. Switching between current sources allows pressure and temperature (flow) values ​​to be obtained, which can then be sent wirelessly to the measurement system.

[0139] Modifications to legacy system implementations

[0140] In one embodiment, the present invention relates to a system adapter for adapting or otherwise improving a measurement system (such as a pressure measurement interface unit), such as a unit that was originally designed only for pressure monitoring. Thus, after adding the adapter, the sensing unit can then support simultaneous pressure and flow sensing with the aid of a guidewire-based probe. The adapter includes a power supply that includes 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 greater than or equal to about 12 volts. In one embodiment, the adapter is a circuit board sized to be mounted in the measurement system.

[0141] One or more circuit elements in the probe interface unit based on the guidewire can be modified or replaced to reach a larger probe excitation voltage based on the guidewire in legacy pressure, FFR, and other intravascular data collection systems. In one embodiment, a power supply component can be added or modified so that the excitation voltage applied to the sensing area is greater than about 10 volts. In another embodiment, a filter can be incorporated wherein the passband is set to remove noise that is scaled to the level of the flow parameter measurement signal.

[0142] Each unit based on pressure sensor has memory, such as EEPROM. In one embodiment, one or more parameters obtained about the probe based on the guide wire are stored in a storage device such as during the manufacture of the probe. In one embodiment, the storage device is attached to the probe based on the guide wire. The storage device can be EEPROM, RFID or other suitable memory. The storage of one or more sensor parameters in the storage device associated with the pressure probe allows to read these parameters on demand. Once read by a suitable scanner or interface device or its parts, before using the probe based on the guide wire to collect pressure and flow information, these parameters can be used to perform the calibration of the probe based on the guide wire.

[0143] In one embodiment, the parameters stored on the probe include a zero-order or baseline temperature, a zero-order or baseline excitation voltage, and a sensitivity factor associated with overtemperature. A pressure versus flow curve can also be an output showing changes in pressure and flow over time and at multiple locations in a blood vessel. The stored memory parameters can be used to scale or calibrate the pressure versus flow curve. The pressure and flow data can also be displayed with image data, such as optical coherence tomography images, ultrasound images, and angiographic images.

[0144] In one embodiment, a memory is placed at the end of the connector that contains individual specific calibration parameters set during production. These stored parameters are used by the guidewire-based probe interface unit software to convert the sampled "raw" voltage into a corrected pressure value in mmHg. Specifically, during the manufacturing process, the pressure sensor is measured in the final measurement site. The purpose is to measure the pressure sensitivity of RA, the temperature sensitivity of RA and RP, and the V POFFS and V TOFFS , sensor current and temperature range balanced bridge. In one embodiment, the relevant parameters are then stored in a memory such as an RFID chip or EEPROM or other memory. In one embodiment, the memory is located in a guidewire-based probe connector.

[0145] Flow measurement

[0146] When using a pressure-based sensor as a hot film anemometer, the sensor array (such as the semiconductor sensor described herein) is heated by an electric current, and the cooling effect of the flowing blood is measured by sampling the voltage across the RP resistor. Figure 4A A circuit is shown in , which shows a suitable configuration of the RP (where the voltage across the RP can be measured) as well as other resistors and electrical connections. This voltage can be used in two related anemometer methods: CTA anemometer method and CVEX anemometer method.

[0147] One consideration associated with hot film anemometer based on pressure sensors is the realization that the electrical signal generated by the associated resistor does not distinguish between flow changes and blood temperature changes. If any unusual blood temperature changes occur, these changes will be interpreted by the system as flow changes. Therefore, other temperature sensors can be used to obtain a feedback loop that monitors the patient's environment as well as the patient's temperature readings. Notwithstanding the above, given the duration of the operation and the time it takes for the blood temperature to change, the blood temperature can generally be considered constant.

[0148] Constant Temperature Angeometry (CTA)

[0149] As an example, in Figure 1A , Figure 1B , Figure 2A and Figure 2C The guidewire-based probe shown in and the components described herein can be used as a flow measurement device as a flow meter in a constant temperature mode, also known as constant temperature anemometer (CTA). The temperature sensitive resistor of the guidewire-based probe sensor chip is heated to a temperature above the ambient temperature by applying a controlled excitation voltage. The resistor is exposed to the surrounding fluid or otherwise communicates with other thermally conductive materials, which respond to changes in blood flow that induce cooling and cause related cooling changes in the sensor. In turn, the flow of fluid will have a variable cooling effect on the resistor. Higher flow rates increase the cooling effect, and lower flow rates reduce cooling. A digital system controls the excitation voltage so that the temperature sensitivity (RP) is stabilized at a predetermined level. Therefore, the excitation voltage becomes a component (measure) of the flow rate.

[0150] The temperature of the RP resistor based pressure sensor is maintained at a constant level, which typically ranges from about 10°C to about 20°C above the blood temperature. This constant temperature is controlled by the bridge excitation voltage. Higher blood flow means a higher cooling effect, resulting in a higher bridge excitation voltage. In contrast, lower flow results in a lower excitation voltage. The excitation voltage thus becomes a component of the flow rate. The Guidewire Based Probe Interface Unit software is controlled from VV TOFFS -V P Voltage extraction R P temperature, and use the temperature as an input to the excitation voltage control system. The control system is also implemented in the guidewire-based probe interface unit software as shown in Figure 5B Proportional (P) controller shown.

[0151] CTA control system implementation

[0152] Figure 5A Shows the use of Figures 1A to 4BThe principle of measuring flow rate using the constant temperature analgeometry (CTA) method is shown in the measurement device. By measuring V TOFFS -V P Bad, such as Figure 5A As shown, by separating this signal from the applied excitation voltage (VEX), a signal that depends only on R P and Figure 4A and 4B The signal of the temperature change of the micro cable resistance ra, rp and rg. Figure 5B This temperature dependent signal in (also called temperature (Temp) signal) is used as input to the VEX control of the DSP software. The control system is designed to maintain a constant temperature signal by controlling the VEX. The constant temperature signal is the same as the constant temperature of the RP, which is the basic concept of CTA, where a specific superheat is created and maintained on the surface (in this case, the RP) that is subjected to the flowing fluid.

[0153] like Figure 5A As shown, for pressure measurement, sampling V A and VP. A is sensitive to temperature and pressure, so one or more signals are used to compensate for the effects of V A -V P In one embodiment, a control system or circuit or signal processing device is used to control the ambient temperature of the pressure difference by using V TOFFS -V P Pressure difference handling V A -V P The voltage difference to V A -V P The voltage difference is temperature compensated. TOFFS -V P is a temperature dependent signal.

[0154] like Figure 5A As shown, there are two measured signal channels, namely the pressure branch (V A and V P )505 and temperature branch (V TOFFS and V P )507. Pressure branch measurement V A and V P The difference between V and V is obtained by measuring the programmable gain 510. The programmable gain 510 amplifies the pressure signal. The gain value can be selected on an individual basis for each guidewire-based probe sensor and is stored in the memory of a given pressure probe or generated from information stored in the memory of a given pressure probe. In one embodiment, the programmable gain value is calibrated so that one analog-to-digital unit (ADU) corresponds to approximately 0.1 mmHg. The analog-to-digital converter (ADC) 520 is responsive to the amplified V A -VP The gain value is read by the signal processing software of the DSP 530, which also loads the gain value in the gain digital-to-analog converter (DAC) circuit, such as Figure 5A shown.

[0155] Figure 5C A control system 580 for an intravascular measurement system based on the CTA operating principle is shown. The control system is programmed to maintain R P The control system controls the temperature by V TOFFS -V P Signal and VEX separation (such as Figure 5B as shown) and using this signal (in Figure 5C The temperature change of the RP is measured using a signal (denoted as measured temperature in the figure) as an input to the control system. The control system compares the input signal to a set point value corresponding to a particular RP overtemperature. The difference between the set point and the measured RP temperature is the error of the system, which is multiplied by a factor k. The result of this multiplication is then added to the excitation voltage from the previous control iteration to produce a new excitation voltage for adjusting the sensing circuit in the probe tip.

[0156] Prior to starting the control system, a set point value based on the temperature of the fluid is determined. Determining the set point is performed by converting a temperature signal measured at a VEX ranging from about 0.5V to about 2V to a Celsius value, the conversion being accomplished using ADU-to-Celsius conversion parameters stored in the memory of the guidewire-based probe. A user-defined overtemperature is then added to the measured fluid temperature to determine the set point in degrees Celsius. The temperature representation of the set point is then converted to an ADU (analog-to-digital unit) value that will be used as the control system set point. The ADU-to-Celsius conversion parameters stored in the intravascular probe memory or another storage location are used to perform the conversion to the set point in the ADU. In one embodiment, the user can set the overtemperature using an interface to the measurement system.

[0157] like Figure 5C As shown, adder ∑ 585 adds the measured temperature 595 with the sign reversed (-1) to the set point temperature 582 to produce an error 587 for the active control system. The error is then multiplied by a factor k, as shown in process step or stage 590, and the multiplication result is then added to the previous excitation voltage 591. As a result of using the scaled error, a new excitation voltage level is generated. This new excitation voltage can then be applied to the intravascular pressure and flow monitoring probe 592. In turn, the probe 592 can be used to sample intravascular data and generate a measured temperature 594.

[0158] exist Figure 5C The measured temperature shown is VTOFFS -V P The voltage is divided by the excitation voltage. This division by the excitation voltage forms a signal that depends only on temperature changes. The set point temperature is stored in a memory based on the pressure sensor. For example, if the memory set point parameter is 10, the system software or control system will maintain the RP temperature at 10°C above the blood temperature. For a 10°C overtemperature, the excitation voltage ranges from about 5 volts to about 7 volts. In one embodiment, higher overtemperatures (greater than 10°C) may require the use of a higher voltage range, i.e., greater than 7 volts. These excitation voltage changes track changes in flow.

[0159] Constant excitation voltage

[0160] In one embodiment, a fixed excitation voltage (such as about 5 volts) is used to perform flow and pressure measurements. In one embodiment, the CVEX-based method does not include a control system algorithm because V TOFFS -V P The voltage is used directly as a measurement of the flow rate measured in the blood vessel. Instead, a flow value calculation algorithm is used without controlling the above according to Figure 5C The VEX changes as described by the control system of FIG. 1 . In contrast, the RP temperature changes with the flow rate. If there is a higher flow rate, this results in a lower RP temperature. Conversely, if there is a lower flow rate, this results in a higher RP temperature. Figure 5D A flow measurement system 600 is shown that processes signals from a guidewire-based probe while using a constant excitation voltage or CVEX.

[0161] like Figure 5D As shown, the DSP software implementation of the present invention receives the Temp signal (sampled V TOFFS -V P VEX (which is constant) is set by the DSP software and converted to an analog signal by a digital-to-analog converter (DAC) 620. The Temp signal is received as input by a flow calculation algorithm 615, which can generate a flow value from the temperature signal.

[0162] Figure 5E FIG. 6 is a schematic diagram of a software implementation for a simultaneous pressure and flow measurement system 650 according to the CVEX method. As shown, the probe interface / measurement system software 660 receives an input differential pressure from an analog-to-digital converter 665. A -V P The difference signal and V TOFFS -V P The difference signal is processed to generate a pressure value that can be displayed as a value or plotted on a console or other display as described herein.TOFFS -V P The difference signal is processed to generate flow values ​​or plots on a console or other display as described herein. These values ​​can be displayed, plotted as a pressure versus flow curve, and otherwise used as input for FFR calculations using a measurement system, or calculated using circuits or processors integrated in the probe itself.

[0163] CVEX and CTA transfer function characteristics and implementation

[0164] A transfer function can be used to convert an applied excitation voltage (when using CTA) or a measured temperature (when using CVEX) to a flow value or a value related to the flow. In one embodiment, the transfer function is determined by subjecting the pressure-based sensor to a known reference flow and plotting a graph of the measured signal versus the reference flow. The reference flow can be generated using a fluid flowing in a closed-loop system, such as water flowing in a loop or a tortuous trough. Fig. 6A and Figure 6B A typical relationship between the measurement signal and the reference flow rate is shown.

[0165] Fig. 6A and Figure 6B Curve fitting performed for CTA and CVEX to obtain appropriate transfer functions are shown, which relate flow rate x and temperature or excitation voltage T(x), respectively. The constants a and b for their individual T(x)=a+b*lnX functions can be determined by subjecting the pressure sensor-based unit to a large number of flow levels and then calibrating the pressure sensor-based unit by curve fitting or other methods. In the CTA context, T(x) outputs the excitation voltage, and in the CVEX context, T(x) outputs the temperature. In either context, the X value is the flow rate or a flow parameter. The transfer function constants (a and b) can be stored on the pressure sensor-based memory.

[0166] Additionally, the inverse of the function a+b*lnX will then be used by the guidewire-based probe interface unit software to calculate flow values ​​as part of the flow calculation algorithm. Flow values ​​can be tracked over time to display points of maximum flow. Points of maximum flow or relative extremes generated using a pressure versus flow plot or other representation can be used to identify points in time or locations along a vessel during which images can be co-registered or measurements obtained, such as a series of FFR measurements corresponding to different time points and flow levels (which span one or more of a maximum, minimum, or relative extreme).

[0167] There are several differences between CTA-based and CVEX-based methods that are worth considering. Fig. 6A and Figure 6BIt is shown that CTA and CVEX share the same type of relationship between flow and measurement unit (a+b*lnX). In addition, both methods measure pulsating flow with the same accuracy (accuracy observed during laboratory testing). Therefore, by considering the flow measurement, the CVEX method and the CTA method can be considered equivalent. In one embodiment, measuring flow and pressure simultaneously appears to benefit from the CVEX method because it simplifies the pressure measurement. The CTA-based method makes pressure measurement more complicated because of 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 synchronously controlling the excitation voltage within narrow error limits.

[0168] Adapt to FFR and other measurement platforms for pressure and flow measurement

[0169] Systems that measure pressure and flow simultaneously can often be performed based on the CVEX principle. Implementing CVEX flow measurement in a pressure sensor based measurement system can be performed using an adapter such as a circuit board or circuit and power supply and some changes in software and control flow.

[0170] From a device or hardware standpoint, it is useful to increase the maximum excitation voltage output to a pressure sensor-based measurement Wheatstone bridge. As part of the process of improving intravascular measurement systems (such as pressure-only measurement systems), in order to monitor both pressure and flow, a guidewire-based probe interface unit board can be equipped with a 12V output power supply unit (PSU) board. In addition, one or more amplifiers in the guidewire-based probe interface unit are biased with +12V and -12V, rather than the conventional + / -5V for pressure sensing.

[0171] In one embodiment, the guidewire-based probe interface software samples V at a sampling rate in the range of approximately 400 Hz to approximately 600 Hz. TOFFS -V P The voltage is sampled. The sampled signal is stored in memory. In one embodiment, the signal is stored in a specific location of the signal data array as a variable generally labeled TEMP. The CVEX implementation converts the differential pressure stored as the TEMP signal and converts it to a flow value using a transfer function as described herein. Figure 5E A software representation of this signal processing is shown in . These hardware and software features are used to provide a system that can use a pressure sensor based system to simultaneously measure pressure and flow using a CVEX based method.

[0172] The flow measurement systems described herein can be implemented using design modifications with respect to specific temperatures. These systems include implementing one or more of cable temperature compensation and flow-insensitive absolute temperature measurement.

[0173] Cable temperature compensation method implementation

[0174] Figure 4A The switches S1 and S2 of the wire-based probe measurement bridge (which are normally "on" during standard wire-based probe interface unit operation) can be used to disconnect any of the branches of the bridge. If S2 is disconnected, the resistance changes (i.e. temperature changes) of the micro cables ra, rp and rg can be detected by the voltage (V TOFFS -V P ) sampling. In contrast, by switching S2 on and off at a specific rate (ranging from about 400 Hz to about 600 Hz) and sampling V during the two S2 states, TOFFS -V P Sampling can extract the temperature signal of the sensor array:

[0175] Sensor temperature = (s2_on_V TOFFS -V P )-k*(S2_disconnect_V TOFFS -V P )

[0176] Where, (S2_ON_V TOFFS -V P ) is the signal sampled during the “on” state of the S2 switching element, (S2_off_V TOFFS -V P ) is the signal sampled during the "off" state of the S2 switching element, and k is a compensation constant associated with a particular probe interface unit. The k value may be stored in memory and accessed as needed by the sensor temperature determination method.

[0177] The cable temperature compensation method (which determines the sensor temperature) removes or reduces the effects of cable temperature changes on the flow signal. Specifically, the method of compensating for cable effects using an "off" signal and an "on" signal creates a signal that is only responsive to sensor temperature changes associated with the sensor array in the end of the intravascular probe. This is desirable because standard handling and clinical use of guidewire-based probes causes temperature changes in the microcable.

[0178] These induced temperature changes can degrade the quality of the uncompensated ("on" state of the S2 switching element) signal as a result of cable resistance changes. TOFFS -V PSignal, therefore the cable temperature compensation method described herein produces a signal that is responsive only to changes in the temperature of the sensor at the end of the probe. In addition, if a stable blood temperature exists, as would typically be the case for a patient resting in a constant temperature environment, then only temperature changes to the sensor will correspond to changes in a flow parameter. In one embodiment, the flow parameter is flow velocity. In another embodiment, the flow parameter is flow rate.

[0179] Flow-Insensitive Absolute Temperature Measurement Implementation

[0180] By using the cable temperature compensation described herein and reducing the excitation voltage to about 0.5V, the system is generated to measure the temperature change of the blood (or the temperature change of any medium in which the probe is inserted). It is advantageous to select an excitation voltage ranging from greater than about 0 volts to about 2 volts, because the excitation voltage causes the sensor array temperature to be approximately the same as the surrounding blood temperature. Therefore, by selecting an excitation voltage that causes the sensor and fluid temperatures to be substantially matched, the pressure and flow monitoring system is insensitive to flow changes. The reason for this is that the flow measurement is based on creating a sensor array temperature in response to an excitation voltage, which can be affected by the cooling of the surrounding fluid as the surrounding fluid flows relative to the probe tip. This allows the flow of blood to be measured, which is completely different from simply measuring the change in blood temperature.

[0181] In one embodiment, the sensor temperature signal defined above is measured at an excitation voltage of 0.5 V. The absolute temperature of the fluid (blood) can then be calculated using the difference relationship between the first constant and the product of the second constant and the sensor temperature:

[0182] Absolute temperature = CD (sensor temperature)

[0183] Where C and D are constants for each interface or processing system or related integrated system that receives data from a given intravascular probe and its sensor array. The sensor temperature mentioned in the above absolute formula can be obtained using the above relationship, where (S2_ON_V TOFFS -V P )-k*(S2_disconnect_V TOFFS -V P ) gives the sensor temperature. In one embodiment, constants C and D are specific to a single intravascular probe and each interface or processing system. In one embodiment, these constants C and D may be encoded in a memory attached to each probe.

[0184] Cable compensation and absolute temperature measurement are useful features in a flow measurement system. In part, this is the case because the signal effects from the micro-cable resistance are removed. In addition, it is helpful to monitor the blood temperature during flow measurement because the flow measurement signal is sensitive to both flow and blood temperature changes. User controls of the measurement system allow the user to manually switch between flow mode and absolute temperature mode.

[0185] FFR measurement and its application

[0186] In one embodiment, one or more pressure versus flow plots are obtained after administration of a congestive medication. In one embodiment, one or more pressure versus flow plots are obtained without administration of a congestive medication. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular measurements are obtained after administration of a congestive medication. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular measurements are obtained without administration of a congestive medication. In one embodiment, one or more FFR, pressure, flow, resistance, or other cardiovascular measurements are obtained during periods of high or maximum flow as determined by measurements from intravascular pressure and flow sensors.

[0187] In one embodiment, based on the ratio of distal pressure to proximal pressure in the blood vessel (P 远侧 / P 近侧 ), an FFR value or related value is obtained. In one embodiment, an FFR value or related value is obtained based on the ratio of maximum flow obstructed / maximum flow unobstructed. These various methods of obtaining flow data (such as flow velocity at multiple points in the cardiovascular system) can be displayed alone or in conjunction with other cardiovascular values ​​as ratios or through other relationships representing patient status.

[0188] In one embodiment, an intravascular probe is moved along the length of an artery and a data set of one or more of pressure measurements, flow parameter measurements, and position measurements is obtained over time. Elements of the data set may be synchronized with each other and registered with IVUS, angiography, OCT, or other data from additional sensors. The data set may be processed to compute measures of distal pressures (such as distal myocardial pressure) and proximal pressures (such as aortic pressure). Multiple FFRs may be obtained from these distal and proximal pressures using the following relationship i value:

[0189] FFR i =P 远侧I / P 近侧I= Maximum flow obstructed / maximum flow unobstructed The i value may be selected as an index into a set of elements obtained for a vessel, such as flow parameters, pressure values, etc., Maximum flow obstructed / maximum flow unobstructed.

[0190] FFR can also be evaluated as the maximum blood flow in the presence of stenosis (first flow) divided by the maximum flow in the absence of stenosis (as a second flow), as described above. According to the flow ratio, the ratio of these maximum flows of obstruction to the maximum flow of non-obstruction produces an FFR value. These flows can be obtained using an intravascular probe as described herein.

[0191] In one embodiment, the FFR values ​​obtained during the period of maximum or minimum flow are evaluated as the determined FFR value based on the events occurring during the respective measurement times and the locations along the blood vessel where these FFR values ​​are obtained. In one embodiment, the minimum FFR value obtained or the FFR value obtained for the maximum flow or the average maximum flow is displayed as the FFR value.

[0192] Pressure and flow plots and traces

[0193] In one embodiment, the present invention involves performing pattern recognition on a pressure versus flow plot or data set generated using a CTA or CVEX based method. The pattern recognition can be performed using a processor in a measurement device or other device that receives data generated from an intravascular pressure and flow probe. In response to the simultaneous collection of pressure and flow data using a guidewire based probe, a pressure versus flow plot can be displayed in real time or near real time. The pattern recognition process can compare pressure versus flow trajectories or patterns or subsets of such curves and correlate them with a condition or patient state of interest.

[0194] In one embodiment, patient data for a healthy population is used to establish a baseline signature, such as a trace or track of a PQ plot, for comparison with individuals seeking diagnostic information. Individual traces may also be obtained for individual patients and compared to subsequent traces to show the efficacy of a given treatment regimen or procedure. Pressure versus flow curves and other plots may also be used, along with FFR values ​​obtained before and during a procedure (such as stenting), to assess the quality and duration of recovery, as described herein.

[0195] The graphical user interface (GUI) of the measurement or display system displays the flow data as a real-time curve in the time domain. Pressure and flow data can be plotted together in real time to produce a Fig. 7APQ plot shown with additional details about pressure and flow ranges. The markers G for green, B for blue, and R for red are used to identify curves, as listed in the legend for the plot or as described herein. G is generally used to indicate curves about the right side of the heart. R is generally used to indicate curves about the left side of the heart. B is generally used to indicate curves about blood pressure versus time.

[0196] In one embodiment, the pressure versus flow curve includes relative extremes, inflection points, maxima, and minima associated with one or more dynamic events, cardiac cycle events, heart disease, degree of stenosis, pre-stent flow, and post-stent flow, degree of recovery after a cardiovascular event, comparison with historical data, and data obtained at different time points. In one embodiment, different time points can be associated with the introduction of one or more drugs or treatment regimens (such as stents).

[0197] In one embodiment, the pressure-versus-flow curve can also be used to calibrate pacemaker function. This can be accomplished by obtaining pressure-versus-flow curves for the patient and monitoring these curves as they change over time and converge to one or more trajectories or shapes. In one embodiment, adjustments to the pacemaker can be made using historical pressure-versus-flow plots and current pressure-versus-flow plots to cause the trajectory to track the pressure-versus-flow plot of a healthy heart. In this way, pacemaker operating parameters can be tuned and calibrated. The pressure-versus-flow curve can also be used to determine pressure readings and flow readings before and after renal denervation therapy to provide efficacy and diagnostic information. In one embodiment, a guidewire-based probe can be placed at various locations in the artery, such as near the trunk and branches, while collecting pressure and flow data. The location where the flow changes from one branch to another can be used to classify a given branch as potentially blocked. These locations can be identified during surgery using IVUS, OCT, angiography, and other imaging modalities.

[0198] Various exemplary curves that can be obtained using pressure and flow sensing probes are discussed in more detail below. These curves are generated using sensor data obtained in an artery, which is obtained at one or more locations using an intravascular probe that includes sensors suitable for simultaneously measuring pressure, temperature, and flow. The sensor data can be used to generate one or more of the following: a signature, a trajectory, a slope, a maximum point, a minimum point, a ratio of measured values, a ratio of measured values ​​to derived values, a ratio of a first derived value to a second derived value, an area, an FFR value, a CFR value, a CFVR value, an IFR value, an IMR value, an indicator, a patient state, or other values ​​and representations of information as described herein.

[0199] The various data elements and curves that evolve and change over time can be used for various diagnostic purposes described herein. In one embodiment, the trajectory or shape or area (or other characteristics) of the pressure versus flow curve can be coordinated with historical data, such as historical data of the patient's age, weight, activity level, and with one or more patient conditions, such as heart attack, damaged valve, and other measurable patient parameters, so that a new patient's pressure versus flow curve can be compared relative to a pressure versus flow curve indicative of a particular patient state to aid in diagnosis.

[0200] Fig. 7A A plot of flow rate versus time is shown using a reference flow probe (identified by R or red or other first marking) and a guidewire-based pressure and flow probe (identified by B or blue or other second marking). Both the reference flow probe and guidewire-based pressure and flow probe embodiments were subjected to pulsating flow in a water circulation loop. The patterns of reference flow and measured flow show a linear relationship between applied flow and measured flow.

[0201] Figure 7B A plot of the measured temperature (flow) signal is shown, which increases in response to a guidewire-based probe being pulled back from a distal left anterior descending artery (dLAD) position to a proximal left anterior descending artery (pLAD) position. The pressure signal is substantially constant during the pullback of the guidewire-based probe through the artery.

[0202] Fig. 8A Plots of pressure and flow versus time obtained for a 40 kg pig using pressure and flow sensing probes are shown. The proximal right coronary artery (pRCA) (right side) is the location monitored using the sensing probe. Pressure and flow are shown on the vertical axis with time along the horizontal axis. The small bump at the bottom of the curve is a small reverse flow. The dashed line shows the pressure values ​​that generally rise and fall in a pattern associated with the flow in the bottom curve. Phases of the pressure and flow curves are plotted relative to the time at the bottom of the curve. Fig. 8A Alignment of the pRCA data shown in .

[0203] Figure 8B A plot of pressure and flow versus time obtained for a 40 kg pig using a pressure and flow sensing probe is shown. pLAD is the location monitored using the sensing probe. Pressure and flow are shown on the vertical axis with time along the horizontal axis. The small bump at the bottom of the curve is a small reverse flow. Fig. 8A In comparison, Figure 8B The phase of the pressure and flow curves is shifted in the figure, where the peak of the pressure signal appears to be shifted to the right relative to the flow signal. Fig. 8A and Figure 8B As shown, the flow peak is located on the right during systole and occurs on the left during diastole.

[0204] Figure 8C A plot of pressure versus flow obtained for a 40 kg pig using a pressure and flow sensing probe is shown. Figure 8C , the proximal right coronary artery (pRCA) is the location monitored using the sensing probe. The loop direction is clockwise. Various points of interest A, B, C, and D are shown. Although any point can be selected as the starting point, the trajectory or loop can be tracked from the lower left corner point A. In one embodiment, the shape or area of ​​the loop can be stored and compared to other loops to identify correlations. The shape or loop can also be monitored for contraction, expansion, displacement, or other changes before, during, or after surgery.

[0205] For example, a path starting at point A (which corresponds to a low flow and low pressure state) can be traced up the loop to point B as pressure increases before moving along the loop to the right, increasing flow to point C along a substantially horizontal path. From point C, as point D is reached along the angled path, pressure and flow decrease until the loop returns to point A. Point A corresponds to a low flow and low pressure state, which characterizes the onset of systole. Point B corresponds to a state of maximum pressure and minimum flow that occurs during systole. Point C corresponds to maximum pressure and flow that occurs during systole. Point D corresponds to a transition state between A and C, with a relative extreme corresponding to the second highest flow during diastole. This flow at point D is reverse flow.

[0206] Fig.8D Plots of pressure and flow versus time obtained for a 40 kg pig using pressure and flow sensing probes are shown. The proximal RCA is the location monitored using the sensing probe. Figure 8C The corresponding points A, B, C and D are Fig.8D These points show the increasing pressure and flow as systole begins, and then the decreasing pressure and flow during diastole after systole.

[0207] Fig. 8E Shown is a plot of pressure versus flow obtained for a 40 kg pig using the pressure and flow sensing probes. Fig.8F Shows the corresponding Fig. 8EPlot of pressure and flow versus time for data from . The proximal left anterior descending coronary artery (pLAD) is the location monitored using the sensing probe. 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, and points A and F occur during diastole. Point A corresponds to the maximum flow during diastole after the contraction of the heart during systole. Point B corresponds to the minimum pressure value that occurs at the beginning of systole. Point C corresponds to a relatively localized increase in pressure before the maximum pressure is reached at point D. Point E corresponds to the closure of the aortic valve and a decrease in pressure in the left ventricle. Therefore, as Fig. 8E As shown, when the pressure drops, blood flow in the left coronary artery increases again.

[0208] Fig.9A Pressure and flow in the pLAD versus time are shown. Fig. 9B Myocardial resistance versus time is shown. Examples of maximum flow and minimum pressure are identified. Myocardial resistance is identified at its minimum at maximum flow. For minimum pressure, myocardial resistance is also identified and plotted. These resistance values ​​can be used to establish time-varying trajectories that are displayed to the user in real time or near real time along with FFR values ​​and other values ​​obtained using intravascular pressure and flow probes that can simultaneously measure the aforementioned parameters. Measurements were obtained using a 40 kg pig.

[0209] Fig. 10A and Fig. 10B The corresponding normal scene ( Fig. 10A ) and abnormal traffic scenarios caused by partial blockage of artificially created edge branches ( Fig. 10B ) plots pressure and flow (top) together with a plot of flow versus time (bottom). The pressure (P) versus flow (Q) trace shown resembles a tilted figure eight or infinity symbol, as in Fig. 10A The pressure versus flow rate is plotted in the upper left corner. In this case ( Fig. 10A The trajectory is basically uniform at any blade. Fig. 10B In the abnormal case of the corresponding plot of , where after the artificial blockage is created, the trajectory is asymmetric, with the left leaflet contracting and the right leaflet expanding. In one embodiment, these can be used as signatures to identify abnormal cardiovascular events. Similarly, Fig. 10A The double peak flow rate versus time curve changes as follows: Fig. 10BIn one embodiment, the amplitude shift and rounding of two peaks to one peak can be used as a signature to identify abnormal cardiovascular events. The plots can also be tracked over time along with other plots and parameter values ​​described herein before, after, and during surgery to inform interested clinicians or other users.

[0210] Coronary blood flow reserve diagnosis system and method

[0211] In part, the present invention relates to methods and systems suitable for determining a coronary blood flow reserve value in response to one or more of intravascular pressure and flow data or data otherwise related thereto. A sensing device (SD) (such as a pressure or flow sensor) can be used to determine a coronary blood flow reserve value that varies over time using thermal convection data. In parallel with the CFR measurement, the same sensing device can be sampled to obtain a distal pressure value Pd, which can be used together with a reference pressure to simultaneously determine an FFR value. The various measurement systems described herein (such as an ICD) can be used to process and display CFR, FFR, and other parameters described herein. The present invention also relates to various user interfaces and associated field modes and inspection modes, through which CFR values ​​and other values ​​can be displayed and plotted.

[0212] Some exemplary sources of pressure data may include pressure sensors, such as electrical or optical pressure transducers. Suitable pressure sensors may be arranged on, within, or otherwise relative to a catheter, such as, for example, a delivery catheter, an intravascular data collection probe, a guidewire, and other suitable devices and systems. CFR and FFR values ​​may be determined simultaneously over time and displayed as numerical values ​​or time-varying curves on a GUI, or CFR and FFR values ​​may be used as inputs to generate other diagnostic data about cardiac system behavior.

[0213] In one embodiment, the present invention relates to an intravascular data collection method. The method allows diagnostic data and information to be collected and generated. In one embodiment, the method includes: tuning or optimizing the temperature signal of an intravascular thermal convection device when in a measurement position of interest; sampling the intravascular thermal convection device to obtain a baseline thermal convection signal value; and sampling the intravascular thermal convection device to obtain a Pd value and a thermal convection device value for running FFR and CFR calculations. The output of the FFR and CFR calculations can be an output on a display of a catheterization laboratory device or other display (such as a touch screen device).

[0214] In part, the present invention relates to methods and systems suitable for simultaneously determining one or more coronary flow reserve (CFR) values ​​and fractional flow reserve (FFR) values ​​using a thermal convection device, such as an intravascular pressure and flow sensor and an intravascular data collection and processing system. In addition, in part, the present invention also relates to determining CFR values ​​using an intravascular probe with a pressure sensor and constant temperature anemometer (CTA) or constant voltage excitation (CVEX) anemometer.

[0215] In one embodiment, CFR is the ratio between the hyperemic absolute flow and the baseline absolute flow. Similarly, in one embodiment, CFVR is defined as the ratio between the hyperemic flow rate and the baseline flow rate. The values ​​of CFR and CFVR are equal. The attached reference to CFR can also be used to implement and display CFVR values. Therefore, the use of the term CFR can also be changed to CFVR as used in this article to describe CFVR embodiments and measurements, which is also within the scope of the present invention.

[0216] Various data collection and analysis systems can be used to obtain information about the coronary system. Data obtained from the blood vessels using the device or derived from intravascular or extravascular measurements associated therewith can be analyzed or displayed to provide correlations and inferences to assist researchers and clinicians. For example, various measurement systems and intravascular probes can be used to determine the blood flow reserve fraction (FFR) and coronary blood flow reserve (CFR). As described herein, a pressure sensor-based device can be used to obtain one or more CFR measurements of a patient.

[0217] In one embodiment, pressure data (Pd) and thermal convection data are collected using an intravascular data collection probe disposed in an artery of a patient. Exemplary intravascular data collection probes include catheter-based or catheter-delivered probes, guidewire-based probes, imaging probes, ablation probes, ultrasound probes, interferometry-based probes, and other suitable data collection probes as described herein.

[0218] In particular, pressure sensors can be used to obtain data to measure flow, thermal convection data, and other cardiac system parameters as described herein. In some embodiments, the systems, methods, and devices described herein are partially related to thermal convection and hot film anemometer techniques, such as constant temperature anemometer (CTA) and constant excitation voltage (CVEX) anemometer. As described in more detail below, relative to existing thermodilution methods, pressure sensors can be advantageously used to sample intravascular data and generate CFR measurements.

[0219] In a background manner, coronary flow reserve measurement can be achieved using a pressure sensor, such as a pressure guidewire or other pressure sensor that can be operated as a thermal dilution device. As part of the conventional technique, a CFR value is obtained by injecting a cold physiological saline solution into the coronary artery of interest. In turn, the temperature measurement capability of the intravascular pressure sensor is used to measure the blood temperature rise time (from the injection of cold saline into the artery to the temperature returning to a specific level). This rise time can be converted into a CFR value.

[0220] Such conventional thermodilution methods suffer from insufficient accuracy and can be cumbersome to implement. For example, the calibration accuracy of an exemplary conventional thermodilution method can result in a CFR value that is less than + / - 30% accurate. The procedure is cumbersome / time consuming because it typically requires multiple injections of a certain mass of saline to generate enough data for the system software to calculate a CFR value.

[0221] The measurement systems, methods and devices described and illustrated herein can be used to obtain a signal that is a measurement of the temperature or power of a pressure sensor chip. The chip resistor is heated by an electric current to produce a specific overtemperature compared to the surrounding fluid (blood). The cooling effect of the blood flowing over the chip resistor is measured directly (as a temperature value) or indirectly (as the electrical power required to keep the temperature of the chip resistor stable).

[0222] Fig.11 An exemplary system 710 suitable for measuring CFR is shown. In addition, the system 710 can also be used to measure CFR values ​​and FFR values ​​simultaneously. Some non-limiting examples of intravascular data collection and analysis systems 710 or components thereof can include RadiAnalyzer, RadiAnalyzer Xpress, Quantien, PressureWire systems (such as Aeris 1, Aeris2 or Certus), optical systems, multimodal systems (such as combined intravascular imaging and pressure monitoring systems), hemodynamic displays with pressure data input.

[0223] In one embodiment, a system (such as a Fig.11A system 710) may include multiple components, such as subsystems and devices. As an example, such a system may include a thermal convection device 760. Examples of such thermal convection devices may include pressure sensor-based devices, such as the pressure sensor-based devices described herein. As a specific example, the thermal convection device may include a pressure sensor Aeris unit suitable for facilitating thermal convection measurements. Such Aeris units may be modified or programmed to use the measurement techniques described herein. In one embodiment, the thermal convection device includes a pressure sensor and is sized and configured to measure distal intravascular pressure and other parameters of interest to measure flow, CFR or FFR or other cardiac system parameters.

[0224] As about Fig.11 As shown in system 710 of , the exemplary thermal convection CFR measurement system may also include a reference pressure device 765. In one embodiment, the reference pressure device can be used to measure a reference pressure, such as aortic pressure. The reference pressure device may include a pressure sensor of a guide catheter or a delivery catheter. Such a reference pressure device also receives proximal pressure values ​​(Pa) (such as aortic pressure values) and sends these pressure values ​​as shown in system 710 as input for FFR calculation.

[0225] The system may also include a signal processing and display unit 730 (such as the Quantien system made by St. Jude Medical), which receives pressure and thermal convection (flow) data from the thermal convection device wirelessly or by means of a cable. Unit 730 also receives pressure data from a reference pressure device (e.g., aortic pressure transducer). In part, embodiments of the present invention relate to various features of pressure sensing devices, measurement systems, and related software suitable for determining ratios based on signals sampled from intravascular data collection probes (such as the probes described and shown herein). Unit 730 may include a display, such as a touch screen display or other display, which is used to output a GUI together with CFR, FFR, and other data of interest measured from the thermal convection device 760 and the reference pressure sensor 765 (such as aortic pressure transducer). In one embodiment, the thermal convection data values ​​are temperature values. These values ​​can be generated based on electrical changes triggered in the thermal convection device. In one embodiment, the thermal convection data values ​​are given in ° C or other temperature units.

[0226] A guidewire-based probe with a semiconductor device including a component that undergoes an electrical change in response to a pressure change is an example of a sensing device that can be used to perform pressure monitoring, flow monitoring, sampling intravascular data for CFR measurement, and sampling intravascular data for FFR measurement. The embodiments described herein support methods for determining CFR values ​​using a thermal convection device, and various systems and methods for performing ratio determination and measurement using a guidewire-based probe of a data collection and analysis system 710 and associated software and electrical components. A wired probe or a wireless probe can be used to transmit Pd, Pa, and thermal convection data from a sensor associated with a given probe.

[0227] System 710 can perform measurement calculations based on signals sampled from the intravascular probe. Alternatively, system 710 can receive signal encoding results of calculations performed using circuits or processing elements arranged in the probe (such as, for example, in the proximal connector of the probe). System 710 can also include software suitable for graphically displaying pressure values, FFR values, CFR values, sampled Pa values, sampled Pd values, moving averages, and other values ​​related to the aforementioned items, control systems, and data analysis and display devices and processors.

[0228] The data collection and analysis system 710 may include a processor (such as a microprocessor), a memory, and one or more software modules, circuits or hardware components (such as a CFR hardware component) or a CFR software module 740. The system 710 may also include an FFR hardware component or an FFR software module 750. These components or software routines are configured to receive intravascular data and simultaneously determine CFR values ​​and FFR values ​​if such information is selected for display on an interface screen. The CFR hardware or software module may include one or more of the methods described herein for determining CFR values ​​using data sampled from a sensing device (SD) and the associated empirically determined functions or mathematical relationships, the sensing device such as the thermal convection device described for a guidewire-based probe for temperature and flow sensing.

[0229] In one embodiment, the thermal convection data is the relative temperature change of a heated measurement resistor, which is a measure of the flow change around the resistor / device. Additional details about systems that can be used to obtain thermal convection data and thermal convection devices based on pressure and flow sensing devices are described and shown herein.

[0230] The CFR measurement is performed in parallel with the FFR measurement. For example, the CFR processing software can be implemented as one or more software routines or methods as part of the Fig.11 The hardware components of the system and the extension of the pressure sensor signal processing software and / or one or more software components running in the device.

[0231] FFR data and thermal convection data CFR process

[0232] about Fig. 12B A set of exemplary steps for a combined FFR and convection CFR measurement process is described. Fig.11 The system and the system described in this article perform these steps. FIG. 13A to FIG. 13D and FIG. 5A to FIG. 5D The relevant graphical user interface screen associated with the output of diagnostic data is shown in FIG.

[0233] exist Fig. 12B In the embodiment of the present invention, a series of exemplary method steps that can be performed to determine one or more CFR values ​​and one or more FFR values ​​for a patient are shown. It is not necessary to perform all steps 10 to 55 in a given embodiment. In addition, some steps can be performed in a different order or can be performed simultaneously with other steps.

[0234] As part of the method, a baseline value of a pressure signal of a sensing device (SD) (such as intravascular pressure in its disk, saline or another buffer) is set or a zero value of the pressure signal is otherwise established (step 10). The SD is advanced and positioned to the catheter opening (but not into the flowing blood) (step 15). The baseline value (zero value) of the SD temperature signal is set (step 20). The SD is advanced to a position distal to the catheter opening and the SD pressure signal (Pd) is equal to the aortic pressure (Pa) signal (step 25). The SD is advanced to a position for CFR and FFR assessment (step 30). The temperature signal is calibrated (tuned) to find a maximum, minimum or other level through voice and / or visual feedback (step 35). The calibration or tuning step can be implemented in software or can be software facilitated by visual or auditory cues that indicate the calibration state presented to the operator when the operator adjusts the control to find the temperature signal level. In one embodiment, tuning or calibration refers to the physical radial movement of the intravascular device in the blood vessel to position the device in the optimal or other desired flow level. The optimum flow rate is usually identified by the temperature signal being positioned at a maximum or minimum level. The temperature signal level is tuned to reach a relative maximum or minimum value or other threshold.

[0235] Still refer to Fig. 12B, the method may further include initiating a data logging session of SD values ​​and setting a CFR baseline (step 40). When the CFR measurement is obtained, in one embodiment, hyperemia is induced (step 45). Thus, in step 45, as an example, the introduction of a hyperemic agent (such as adenosine) is performed with respect to the patient being monitored to determine the CFR value and the FFR value. Verification of pressure equalization and return of the flow signal to baseline is performed (step 50). Finally, in one embodiment, once a set of desired sampling probe values ​​has been obtained or a concurrent diagnosis or treatment has been inferred, the data logging session is terminated or stopped from occurring (step 55). In one embodiment, the baseline level is level 1 or another established baseline value.

[0236] FFR measurement systems (such as the Quantien system or Fig.11 A graphical user interface (GUI) of the system may include one or more processors or control systems for providing user controls for zeroing the pressure sensor temperature signal. Additionally, such user controls may be used to set a CFR baseline value, as well as new graphical windows for signal tuning and CFR traces. The system will also be extended with a sound interface / speaker for audio tuning steps.

[0237] In various screenshots, Fig.11 One or more areas or panels of a GUI or other display output of a system of the invention or other systems described and illustrated herein showing recorded measurements for simultaneous FFR and CFR assessment. For example, simultaneous display of FFR data and CFR data is shown using Fv / Fv-B (flow / flow-to-baseline ratio), which, in review mode, along with the FFR value, is the output from the CFR calculation displayed in various interface graphs.

[0238] In part, the present invention includes various features that depict to the user the development and new diagnostic information and methodology regarding CFR and FFR. One such feature is a process for determining CFR values ​​based on the following relationship CFR = b^((x_hyperemia - x_baseline) / c). Additionally, the CFR relationship can be evaluated based on a pressure sensor temperature or power signal measured from an intravascular pressure probe such as herein. As referred to herein Fig.11 As stated, it is advantageous to run the CFR software-based method or hardware component 740 in parallel with the pressure sensor pressure signal processing (as part of the FFR software-based method or hardware component 750) to facilitate simultaneous FFR and CFR measurements and subsequent simultaneous display of the FFR and CFR values. The method steps described herein (such as those with respect to Fig. 12A and Fig. 12B The method flow and associated user interface, and plotting of CFR data and simultaneous plotting of FFR and CFR changes over time) are additional features for providing enhanced diagnostic information to the user.

[0239] Fig.14 The performance of CFR measurements performed using thermal convection flow measurement on the Aeris2 platform using a PressureWire 8th generation unit provided by St. Jude Medical is shown compared to a baseline CFR of known CFR values ​​used as comparison. Measurements were performed in a 3 mm tube at three different positions, shown as red (position 1), blue (position 2), and green (position 3). In one embodiment, during the measurement, the PressureWire is rotated and the maximum flow signal level is determined before each CFR measurement. The results show that for all positions, the maximum deviation is within 10%. This compares favorably to the 30% error tolerance specified for PressureWire CFR measurements using the thermodilution method.

[0240] Visual representation of intravascular and other cardiac system data

[0241] exist FIG. 13A to FIG. 13D and FIG. 15A to FIG. 15D Various exemplary graphical user interfaces (GUIs) or display outputs are shown in , which include data sets generated using intravascular measurements, such as pressure measurements, temperature measurements, flow measurements, or one or more of measurements derived therefrom or related thereto. In one embodiment, there are multiple modes for intravascular data processing and display system outputs. By way of example, the live mode and the inspection mode are discussed in more detail below.

[0242] Live Mode - GUI

[0243] Fig.13A An exemplary GUI 805 is shown in live mode, where data is displayed as it is sampled by an intravascular probe and processed by a measurement system (such as system 710 or other ICD described herein). The GUI is typically displayed on a touch screen, and the various elements on the interface can be activated and deactivated and otherwise interacted with to change the display, calibrate the system, and make other modifications. In the live mode shown, real-time data curves and values ​​are displayed, which provide real-time insight to a user examining such data, such as may be the case before, during, or after a diagnostic procedure for another treatment.

[0244] like Fig.13AAs shown, various charts or plots about measured cardiac system data can be shown. The upper graphical window shows the phase Pd (using one color, such as green, or the second marker), Pa (using another color, such as red, or the first marker), and their respective averages. The white phase curve 807 is the thermal convection (flow) data, which is mapped to the current flow ratio (see numerical information below). The average value of the phase curve matches the current flow ratio (1.88). The lower graphical window shows a colored line 808, such as a yellow line, or another marker, reflecting the current Pd / Pa value (0.98). The panel on the right shows the following numerical information from top to bottom:

[0245] • Pa average values, where Pa maximum and Pa minimum values ​​are shown with smaller numbers.

[0246] • Pd average values, where Pd maximum and Pd minimum values ​​are shown with smaller numbers.

[0247] Pd / Pa value, based on the average of Pd and Pa.

[0248] Fv / Fv-B (flow / flow-baseline ratio), which is the output from the CFR calculation. In one embodiment, in field mode, this value is not referred to as CFR because the definition of CFR is the ratio of flow at maximum hyperemia relative to baseline flow. These definitions can be modified and changed based on the desires of the user of the system. In one embodiment, maximum hyperemia only exists during a very short portion of the measurement cycle. In one embodiment, Pd / Pa is not identified as FFR in field mode.

[0249] Fig.13A The GUI includes various user control buttons Rec, Equalize, Patient, Live, Review, and Archive buttons and menus. Fig.13A The exemplary GUI 805 also includes new controls and buttons for the Enable CFR control interface. The Enable CFR control can be adjusted by the user to enable and disable the FFR+CFR mode, i.e., the user can select between the FFR mode and the FFR+CFR mode. In various embodiments, the GUI shown in this article is implemented using a touch screen or other control and input device.

[0250] Baseline Control Fig.13A) can be used to open a new menu where the user can choose between Tune and Set Baseline. In turn, the Tune control can be used to activate the thermal convection signal tuning, using visual information (graph) and audio (sound signal) to provide the user with the opportunity to optimize the thermal convection signal, i.e., position the device in the best vascular position. The Set Baseline control can be used to instruct the software to store the current average value of the thermal convection signal as T bas , for use in CFR calculations.

[0251] Check Mode

[0252] exist Fig. 13B , Fig. 13C and Fig.13D In the inspection mode shown in FIG, the measurement record is presented. The screen shows how the pressure and flow ratios start at 1 (baseline flow) and then shift to their respective hyperemia levels when hyperemia begins, i.e., for Fig. 13B , a pressure ratio of about 0.8 and a flow ratio of 5.0. Note that the flow ratio specifications are shown on the right hand side of the top curve window, ranging from 0.0 to 10.0. Assuming the user slides the cursor over the record to identify the maximum hyperemia (this is when the two ratios become FFR and CFR), on the review screen these ratios are referred to as FFR and CFR.

[0253] CFR Determination - Thermal Convection Data

[0254] As described herein, multiple possible transfer functions from blood flow values ​​to measured pressure sensor signals are listed. In one embodiment, a transfer of the following form is used: x=a+c*logbQ, where the base b of the logarithm is not specified, x is the measured pressure sensor temperature signal or chip power, a is the offset value, c is the gain factor, and Q is the value of the blood flow. Both a and c depend on the position of the pressure sensor chip in the blood vessel. The inverse of the function is used to calculate the flow value using the measured pressure sensor signal: Q=b^((xa) / c). CFR (Q_congestion / Q_baseline) can then be calculated as b^((x_congestion-x_baseline) / c), as described in more detail herein. In one implementation, the offset value (a) is not necessary for the CFR calculation.

[0255] The CFR calculation is based on one of the transfer functions mentioned above, namely:

[0256] T=a+c*lnQ (1)

[0257] 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 that depend on the device and the location of the thermal convection device inside the flow tube. To calculate the flow value, given the measured thermal convection device temperature, the inverse of (1) is used:

[0258]

[0259] In one embodiment, CFR is defined as:

[0260]

[0261] Among them, Q hyp is the congested coronary flow and Q bas is the baseline (resting) coronary flow. The CFR index is therefore the value of the maximum achievable blood flow growth ratio of the coronary system.

[0262] By substituting (2) into (3), we obtain:

[0263]

[0264] Among them, T hyp is the temperature measured under hyperemic flow, and T bas is the temperature measured at baseline flow. This requires that the thermal convection device be kept stable at a specific measurement location during baseline and hyperemic flows (otherwise, the constants a and c will be invalid for both hyperemic and baseline). FIG. 15A to FIG. 15D Hyperemia can be visualized as a negative plateau shown in the bottom window of the FFR data plot and on the screen for the Fv / Fv-B (flow / flow-to-baseline ratio) plot (see Fig.15A ) shows the positive flat area in the middle. Figure 5A The vertical lines shown around the left third of the screenshot indicate the onset of congestion. A simplification of (4) using the logarithmic law gives:

[0265]

[0266] Further simplification leads to the final CFR function, as used by CFR calculation software:

[0267]

[0268] Note: The constant a is not necessary to calculate CFR. However, the constant c is critical and specific to the thermal convection device and its location in the flow vessel. Also note: The CFR value is the ratio of the flow rate relative to the baseline flow rate, meaning that T bas The value acts as a constant during a specific CFR calculation. bas The value of is provided indirectly by the user; when the coronary flow is at a static level and the operator has placed the thermal convection device in the optimal measurement position, the GUI button Set Baseline is pressed and the software stores the current thermal convection value (average) as T bas .

[0269] The function can be written in a more general form by using the base of any logarithm (b) instead of the base of the natural logarithm (e):

[0270]

[0271] Intravascular data collection devices may be used to generate and receive signals including diagnostic information about the blood vessel in which the device is used. These 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.

[0272] In part, the present invention relates to intravascular data collection systems and related methods by which a processor-based system can transform or analyze intravascular data collected by an intravascular probe. The results of such analysis and transformation can be displayed to an end user in various presentations, such as a display that is in communication with or is part of a system such as a pressure monitoring system or an intravascular data collection system. Examples of such systems are, for example, Figures 1A to 2B , FIG. 5A to FIG. 5E , Fig.11 , FIG. 13A to FIG. 13D , FIG. 15A to FIG. 15D , and as otherwise shown in whole or in part in other drawings.

[0273] In one embodiment, a display console is used to display a user interface (such as a touch screen interface) and one or more of flow rate, maximum flow, minimum flow, flow threshold, relative extremes of flow, 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 in one embodiment, one or more indicators of myocardial resistance (IMR) values ​​in one or more panels, user interface areas, or as values ​​or as plots or charts about system components. The display device, console or cart or other housing to which it is attached or in electrical or wireless communication therewith may include one or more microprocessors for performing one or more of the steps described herein and processing intravascular signals from the probes listed herein.

[0274] These drawings and user interface screens can be used along with intravascular and angiographic images to make stent decisions, identify regions of interest from a diagnostic standpoint, and inform other cardiac system treatment decisions as a diagnostic tool.

[0275] In one embodiment, a user of the systems, methods, and displays disclosed herein can examine a given display of FFR values ​​and CFR values ​​over time before, during, or after surgery to diagnose stenosis severity, stenosis location, guide treatment strategy, evaluate treatment effectiveness, and assess the need for additional postoperative treatment.

[0276] Flow peak / flow threshold measurement and assessment implementation method

[0277] Pressure or flow sensors or other sensing devices can be used in conjunction with a system (such as an integrated cardiology display or other system described herein) to determine one or more categories of time-varying intravascular data using thermal convection data or flow data obtained using a flow sensor or from other measurements related to flow data. In addition to thermal convection-based sensors, mechanical sensors, optical sensors, and other flow sensors can also be used. The system can include a signal processing and display unit (such as a RadiAnalyzer system, RadiAnalyzer Xpress system, Quantien system, Aeris system, Prestige guidewire-based probe system, Pressure and flow systems, and other intravascular pressure sensing or FFR determination devices and systems). In one embodiment, a pressure or flow sensor is used that is part of an intravascular probe. The system may also include or communicate with a reference pressure device, such as a catheter suitable for measuring proximal or distal pressure values. In one embodiment, the reference pressure device can be used to measure a reference pressure, such as aortic pressure. The reference pressure device may include a pressure sensor for a guide or delivery catheter.

[0278] The same sensing device may be sampled to obtain distal pressure values ​​Pd, which may be used 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 sends these proximal pressure values ​​(Pa) for subsequent analysis and calculations to a suitable system, such as described herein and as described in Figures 1A to 2B , FIG. 5A to FIG. 5E , Fig.11 , FIG. 13A to FIG. 13D , FIG. 15A to FIG. 15D The system is shown in an exemplary embodiment.

[0279] In one aspect, the present invention relates to using acquired intravascular data to detect, as non-limiting examples, a flow threshold (such as a flow peak or other relative extreme), an inflection point, a first derived value, or a second derived value during a cardiac cycle using one or more of the techniques described herein. In turn, a detected flow threshold (such as a flow peak (or other value or point)) can be selected as an indicator for a measurement system, such as for calculating a pressure ratio / difference. On a per cardiac cycle basis, reference is made to Fig.16 , Fig.17A , Fig. 17B and exemplary pressure and flow curves along with plots of Pa and Pd values ​​describe additional details regarding exemplary process steps.

[0280] In part, embodiments of the present invention relate to various features of a pressure sensing device, a measurement system, and its associated software adapted to determine a ratio based on signals sampled from an intravascular data collection probe. These signals (which may be various values, such as pressure or flow thresholds (specified by a user via an interface or automatically identified by the measurement system)) are used to select a point or time period during the cardiac cycle. The point may be the maximum value of a set of flow values ​​obtained using the probe. The selected point or time period is used to perform a measurement or select a previously obtained measurement, which includes a distal pressure value or other parameter, including but not limited to flow rate, maximum flow, minimum flow, flow threshold, relative extremes of flow, one or more blood flow reserve fraction (FFR) values, coronary blood flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous blood flow reserve (IFR) values, and one or more indicators of myocardial resistance (IMR) values. The flow threshold may be specified as a level greater than or equal to the measurement level of the flow, which is classified as peak flow or high flow.

[0281] Alternatively, the maximum flow value or absolute value of the measured flow can be identified as a flow threshold or flow peak, at which point in the cardiac cycle one or more pressure values ​​or other intravascular parameters of interest are measured. The selection of the flow threshold provides such a point, and the pressure difference, flow value, or other values ​​described herein, such as statistical values ​​and other indicators, relative to the point can be obtained using the sensing device. The diagnostic data collected at each flow threshold (such as a peak or maximum flow) can then be displayed as a value, plotted or otherwise processed and used to generate a correlation value, which can then be displayed or plotted.

[0282] Diagnostic methods and related thermal convection systems and devices suitable for performing stenosis assessment in coronary arteries are described herein. These systems and methods can be used to detect flow peaks (or other values ​​or points as described herein), which can be used as a guide to identify time points or events in the cardiac cycle of interest. These time points or events can be used as a basis for measuring pressure ratio differences during the events or time points. These methods and systems can be used to perform unaemic measurements, such as unaemic or resting FFR values.

[0283] In some of the currently used techniques for determining FFR independently of flow data or other indicators associated with flow peaks or other time points in the cardiac cycle, assumptions are made to determine FFR values, such as defining areas where high flow typically occurs. In contrast to such definition methods, rather than simply specifying such areas selected for data collection, velocimetry-based or other flow measurement-based systems and methods as described herein can be used to accurately measure when high flow or peak flow occurs or another indicator related to or derived using such measured flow values. In some embodiments, this is referred to as peak flow, which can correspond to the occurrence of maximum blood flow, which is associated with a maximum blood flow peak or other relative extreme during the cardiac cycle.

[0284] The location of interest (at a flow threshold, such as a 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 ratio of the cycle is not determined by preselecting areas based on expectations about the behavior of the heart during systole and diastole. The pressure drop can be measured at rest and / or during hyperemia. The occurrence of the flow peak can be located anywhere in the cardiac cycle, and the ratio of the distal pressure (Pd) and the aortic pressure (Pa) can be measured at that point (or several points / samples nearby at that point). If the pressure drop is of interest, the difference (Pa-Pd) is measured at the same point or points. As Fig.18 As shown, for the cardiac cycle shown, P 大动脉 The curve shows the Pa value at peak flow and the Pd value at the vertical double-headed arrow. On a per cardiac cycle basis, these values ​​can be found at peak flow or other specified flow thresholds and used to calculate FFR, pressure difference and other values. In one embodiment, over multiple heartbeats, the arithmetic mean or other statistical or data indicators (mean, median, mode, standard deviation, etc.) of the measurements are calculated. At peak flow or other flow threshold, the ratio is Pd / Pa. At baseline (if hyperemia is not introduced), this is the lowest Pd / Pa in the cardiac cycle and represents a resting indicator without hyperemia.

[0285] Fig.16A series of method steps for a diagnostic method (such as a vascular or stenosis assessment method) that uses flow thresholds and other measured intravascular parameters. As one step of the method, a flow threshold detection is performed using an interface or other intravascular measurement system and one or more sensing devices in a non-congested state (or in a congested state) (step A1). Therefore, the sensing device or system component can output one or more peak flow values ​​(or other one or more identification values) (step A2). In addition, in response to the occurrence of the identified peak flow value (or other one or more identification values) or when the identified peak flow value (or other one or more identification values) occurs, the system and associated control logic can determine a pressure ratio and / or a pressure difference (step A3). Using such a pressure ratio or pressure difference, the system can generate a statistical indicator or other indicator (such as an arithmetic mean, mode, deviation, or other indicator or statistical value) of the pressure ratio, pressure difference, or both over one or more heartbeats (step A4).

[0286] In turn, the system may then display or output diagnostic information (step A5), such as a plot or ratio or difference obtained at a flow threshold value, such as a peak flow or maximum flow. The flow value may be generated using an intravascular sensor and may be used to provide input to the system to select a flow threshold value. The system may display one or more of the numerical values ​​of the pressure ratio (Pd / Pa) or values ​​related thereto at an identification value, such as a maximum flow or other identification value (step A6). If the data is collected in a non-congested state, the system may display / classify the output as a non-congested resting baseline (step A6-1). If a hyperemic agent is used, the system may display / classify the output as hyperemic data (step A6-2). In addition, the system may display one or more of the numerical values ​​of the pressure difference value at an identification value, such as a maximum flow or other identification value (step A7). The system may display / classify the output as a non-congested resting baseline (step 7-1). The system may display / classify the output as hyperemic data (step 7-2).

[0287] Fig.17A Another embodiment of a diagnostic method for pressure value ratios is suitable for use with one or more of the pressure and flow sensing systems described herein. Fig.17A, as shown, the various steps regarding the Pd / Pa ratio are outlined. At an initial time, the system is used to send / provide intravascular data about 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 a cardiovascular event is performed (step B2). Determining the ratio of distal pressure to aortic pressure (pd / pa) during the first flow threshold is performed (step B3). In addition, the system can be configured to determine one or more indicators for a pressure ratio for multiple time periods or cardiovascular events (step B4). The system can then display one or more of pd / pa, a determined indicator, a determined flow value, or a value derived therefrom as a numerical value or plotted against time or on a per cardiovascular event basis (step B5). Fig.18 Shown from Fig.17A An exemplary output display of the method of , or a plot suitable for showing flow thresholds and the Pa and Pd values ​​found at such thresholds (such as the Pa and Pd values ​​shown along vertical line A for the first cardiac cycle A).

[0288] Fig. 17B Another embodiment of a diagnostic method for pressure value ratios is suitable for use with one or more of the pressure and flow sensing systems described herein. Fig. 17B In, various steps of a diagnostic method are summarized, which involves a pressure difference for an intravascular pressure value and another pressure value of interest. The system can be used to perform a step of sending / providing intravascular data about a vessel of interest (step B1). As a further step, determining a first flow value at a first flow threshold during a first period or cardiovascular event can be performed (step B2). Flow values ​​measured using a flow sensor (such as using temperature and voltage as described herein) can be used to select a flow threshold at which a measurement value will be obtained. Determining a pressure difference (pa-pd) from aortic pressure to distal pressure during the first flow threshold can be performed (step C1).

[0289] As a further step, determining one or more indicators for the pressure difference for a plurality of time periods or cardiovascular events (step C2) may be performed, such as by user selection or pre-defined selection in the system. The system displays one or more of the determined indicators, the determined flow values, or values ​​derived therefrom as numerical values ​​or plotted against time or on a per cardiovascular event basis (step C3). Fig.18 Shows Fig. 17B An exemplary output of the method is shown.

[0290] about Fig.18 , such as through Fig.16 , Fig.17A and Fig. 17BOne or more of the methods of , using measured intravascular data to generate two plots or traces. Plot 910 (top of the figure) and plot 920 (bottom of the figure) respectively show pressure versus time and flow value versus time for cardiac cycles AE. That is, a series of pressure curves versus time are shown over multiple cardiac cycles. In the top figure (plot 910), the solid line corresponds to the upper curve and shows that the aortic pressure rises and falls over time as the heart goes through a series of cardiac cycles. The lower pressure curve corresponds to the distal pressure measured in the blood vessel, which is shown by the dotted lines 100A, 100B, 100C, 100D and 100E corresponding to the flow threshold. The Pd value and the Pa value can be found at the intersection of the double-headed arrows and used to determine a first parameter (such as Pd-Pa or Pd / Pa) or a second parameter that is also related to the first parameter.

[0291] Each vertical dashed line labeled A to E indicates a flow threshold at which data is collected and diagnostic data is generated on a per cardiac cycle basis. The vertical line shown corresponds to the maximum flow. However, other flow thresholds may be used, such as X% of the maximum flow, where X ranges from about 1 to about 100. There are five cardiac cycles AE shown. The pressure difference shown by the double-headed arrow and identified as PD-A, PD-B, PD-C, PD-D, and PD-E is the pressure difference or pressure ratio determined at the associated time segment shown by the vertical dashed line, which corresponds to the flow threshold selected by the system. As shown in this article, the maximum flow or peak flow is the basis for the flow threshold, which is used to determine the location of the measured pressure ratio or pressure difference. On a per cycle basis, the flow threshold shown by the vertical line can be selected as the maximum flow value, as determined using the temperature-based flow measurement or other flow sensor described herein.

[0292] For the 5 heartbeats shown, the double-headed vertical arrow corresponds to the difference between the first pressure and the second pressure. The double-headed arrow is aligned with the vertical dashed line, which spans the upper figure and also continues downward to the lower figure. These dashed lines indicate the occurrence of flow thresholds (such as peak flow). These dashed lines can be set using a control system and other flow thresholds of interest (such as measured flow values ​​or other values ​​related thereto). The diagnostic values ​​or their plots that can be determined and displayed at the flow thresholds include, but are not limited to, one or more blood flow reserve fractions (FFR) values, coronary blood flow reserve (CFR) values, coronary flow velocity reserve (CFVR) values, instantaneous blood flow reserve (IFR) values, and one or more indicators of myocardial resistance (IMR) values.

[0293] The various pressure differences and pressure issues described herein can be displayed as numerical values ​​used during diagnostic processes or other processes. These differences and ratios can also be used to generate various indicators, such as statistical values ​​and other indicators. Examples of such statistical values ​​include weighted averages, means, arithmetic means, wave mode frequencies, medians, standard deviations from parameters such as baseline (whether hyperemia or vice versa), and other statistical values ​​about intravascular and coronary system parameters.

[0294] Non-limiting software features and implementations for implementing pressure and flow related data collection and analysis methods and systems

[0295] The following description is intended to provide an overview of the equipment hardware and other operating components suitable for performing the method of the present invention described herein. This description is not intended to limit applicable environment or scope of the present invention. Similarly, hardware and other operating components may be suitable as parts of the above-mentioned device. Other system configurations may be utilized to practice the present invention, including personal computers, microprocessor systems, microprocessor-based or programmable electronic devices, network PCs, minicomputers, mainframe computers, etc. The present invention may also be practiced in a distributed computing environment (such as in different compartments of a catheter or catheter room) by a remote measurement device execution task linked by a communication network.

[0296] Some parts of the detailed description are presented according to algorithms and symbolic representations of operations on data bits in computer memory. These algorithmic descriptions and representations can be used by technicians in computer and software related fields. In one embodiment, algorithms are here and generally conceived as a series of self-consistent operations that lead to a desired result. The operations performed as method steps or described in addition herein are operations that require physical manipulation of physical quantities. Typically, although not necessarily, these quantities take the form of electrical or magnetic signals that can be stored, transmitted, combined, transformed, compared, and otherwise manipulated.

[0297] Unless explicitly stated otherwise, as will be apparent from the following discussion, it is to be understood that throughout the specification, discussions utilizing terms such as "processing" or "computing" or "searching" or "detecting" or "measuring" or "calculating" or "comparing" or "generating" or "sensing" or "determining" or "displaying" or the like, or Boolean logic or other set-related operations, etc., refer to the actions and processes of a computer system or electronic device that manipulates data represented as physical (electronic) quantities within the computer system's or electronic device's registers and memories and transforms that data into other data similarly represented as physical quantities within an electronic memory or register or other such information storage, transmission or display device.

[0298] In some embodiments, the present invention also relates to an apparatus for performing the operations described herein. The apparatus may be specifically constructed for the desired purpose, or the apparatus may include a general-purpose computer that is selectively enabled or reconfigured by a computer program stored in the computer. Various circuits and components thereof may be used to perform some of the data collection and transformation and processing described herein.

[0299] The algorithms and displays presented herein are not inherently related to any particular computer or other device. Various general purpose systems may be used in conjunction with the programs taught herein, or it may prove convenient to construct more specialized devices to perform the required method steps. The structures required for a variety of these systems will emerge from the following description. In addition, the present invention is not described with reference to any particular programming language, and therefore various embodiments may be implemented using a variety of programming languages.

[0300] Embodiments of the invention may be embodied in many different forms, including but not limited to computer program logic used with a processor (e.g., a microprocessor, a microcontroller, a digital signal processor, or a general purpose computer), programmable logic used 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 components including any combination of these components. In a typical embodiment of the invention, some or all of the processing of data collected using an OCT probe and a processor-based system is implemented as a set of computer program instructions that are converted into a computer executable form, themselves stored in 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 transformed 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; such as displaying and plotting data and parameters as described herein in an area of ​​a GUI, and otherwise performing analysis and comparison based on pressure versus flow curves and flow measurements, and other features and embodiments described above. Data and parameters suitable for display as a plotted curve, value, or another representation in a graphical user interface may include, but are not limited to, 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, a flow threshold, an average of flow thresholds, and an indicator of myocardial resistance (IMR) value.

[0301] The computer program logic that realizes all or part of the functions previously described herein can be embodied in various forms, including but not limited to source code form, computer executable form, and various intermediate forms (forms generated by, for example, assemblers, compilers, linkers, or locators). Source code can include a series of computer program instructions implemented in any of various programming languages ​​(e.g., object code, assembly language, or high-level languages, such as Fortran, C, C++, JAVA, or HTML), and the above-mentioned various programming languages ​​are used together with various operating systems or operating environments. Source code can define and use various data structures and communication messages. Source code can be in computer executable form (e.g., with the help of annotators), or source code can be converted (with the help of translators, assemblers, or compilers) into computer executable form.

[0302] A computer program may be permanently or temporarily fixed in any form (e.g., source code form, computer executable form, or intermediate form) in a tangible storage medium such as a semiconductor storage device (e.g., RAM, ROM, PROM, EEPROM, or flash-programmable RAM), a magnetic storage device (e.g., a magnetic disk or fixed hard disk), an optical storage device (e.g., a CD-ROM), a PC card (e.g., a PCMCIA card), or other storage device. A computer program may be fixed in any form in a signal that can be sent 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. A computer program may be distributed in any form as a removable storage medium with printed or electronic documentation (e.g., shrink-wrapped software), pre-loaded with a computer system (e.g., on a system ROM or fixed hard disk), or distributed over a communication system (e.g., the Internet or World Wide Web) from a server or electronic bulletin board.

[0303] Hardware logic that implements all or part of the functionality previously described herein (including programmable logic for use with programmable logic devices) can be designed using traditional manual methods, or can be designed, captured, simulated, or documented electronically using various 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).

[0304] Programmable logic may be permanently or temporarily fixed in a tangible storage medium, such as a semiconductor storage device (e.g., RAM, ROM, PROM, EEPROM, or flash-programmable RAM), a magnetic storage device (e.g., a magnetic disk or fixed hard disk), an optical storage device (e.g., a CD-ROM), or other storage device. Programmable logic may be fixed in a signal that can be sent 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. Programmable logic may be distributed as a removable storage medium with printed or electronic documentation (e.g., shrink-wrapped software), preloaded with a computer system (e.g., on a system ROM or fixed hard disk), or distributed over a communication system (e.g., the Internet or World Wide Web) from a server or electronic bulletin board.

[0305] Various examples of suitable processing modules are discussed in more detail below. As used herein, module refers to software, hardware, or firmware suitable for performing specific data processing or data transmission tasks. Typically, in a preferred embodiment, module refers to a software routine, program, or other memory resident application suitable for receiving, transforming, routing, and processing instructions or various types of data, such as resistance changes, probe data based on guidewires, temperature data, intravascular flow data, intravascular pressure data, transfer function output calibration data, excitation voltage, and other information of interest.

[0306] The computers and computer systems described herein may include operatively associated computer-readable media, such as memory for storing software applications used in obtaining, processing, storing and / or transmitting data. It is understood that such memory may be internal, external, remote or local relative to the computer or computer system to which it is operatively associated.

[0307] The memory may also include any component 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 Disc), a CD (Compact Disc), a memory stick, a flash memory, a ROM,

[0308] (Read Only Memory), RAM (Random Access Memory), DRAM (Dynamic Random Access Memory), PROM

[0309] (Programmable ROM), EEPROM (Extended Erasable PROM), and / or other similar computer readable media.

[0310] Typically, the computer-readable storage medium associated with the embodiments of the present invention described herein may include any storage medium capable of storing instructions executed by a programmable device. Where applicable, the method steps described herein may be embodied or executed as instructions stored on a computer-readable storage medium or storage medium. According to embodiments of the present invention, these instructions may be software embodied in various programming languages, various programming languages ​​such as C++, C, Java and / or various other types of software programming languages ​​applicable to create instructions.

[0311] Storage media may be non-volatile or include non-volatile devices. Thus, non-volatile storage media or non-volatile devices may include tangible devices, meaning that the device has a specific material form, but the device can change its physical state. Thus, for example, non-volatile means that the device remains tangible regardless of how the state changes.

[0312] The aspects, embodiments, features and examples of the present invention are to be considered exemplary in all respects and are not intended to limit the present invention, the scope of which is limited only by the claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art without departing from the spirit and scope of the present invention as claimed.

[0313] The use of headings and sections in this application is not intended to limit the invention; each section may apply to any aspect, embodiment, or feature of the invention.

[0314] Throughout this application, where a composition is described as having, including, or comprising specific components, or where a process is described as having, including, or comprising specific process steps, it is contemplated that the composition of the present teachings also substantially includes or comprises the listed components, and that the process of the present teachings also substantially includes or comprises the listed process steps.

[0315] In the present application, when an element or component is said to be included in a list of listed elements or components and / or selected from the list, it should be understood that the element or component can be any one of the listed elements or components and can be selected from a group consisting of two or more of the listed elements or components. In addition, it should be understood that the elements and / or features of the composition, device or method described herein can be combined in various ways without departing from the spirit and scope of the present teachings, whether explicit or implicit, herein.

[0316] Use of the terms "including," "comprising," or "having" should generally be construed as open ended and non-limiting, unless expressly stated otherwise.

[0317] The use of the singular herein includes the plural (and vice versa), unless expressly stated otherwise. In addition, the singular forms "a", "an", and "the" include the plural forms unless the context clearly indicates otherwise. Furthermore, where the term "about" is used before a value, the present teachings also include the specific value itself, unless expressly stated otherwise.

[0318] It should be understood that the order of steps or the order in which certain actions are performed is not important, as long as the present teachings remain operable. In addition, two or more steps or actions may be performed simultaneously.

[0319] In the case of providing a certain range of values ​​or a series of values, each intermediate value between the upper and lower limits of the certain range of values ​​or a series of values ​​is considered separately and is included in the present invention, as if each value is clearly listed in this article. In addition, the smaller range between and including the upper and lower limits of a given range is considered and is included in the present invention. The list of exemplary values ​​or ranges is not to abandon other values ​​or ranges between and including the upper and lower limits of a given range.

[0320] It should be understood that in order to clearly understand the present invention, the drawings and description of the present invention have been simplified to illustrate relevant elements, while eliminating other elements for simplicity. However, those of ordinary skill in the present invention will recognize that these elements and other elements may be desirable. However, since such elements are well known in the art and since these elements do not promote a better understanding of the present invention, a discussion of such elements is not provided herein. It should be understood that the drawings are presented for illustrative purposes and are not intended to be construction drawings. Omitted details and modifications or alternative embodiments are within the scope of those of ordinary skill in the art.

[0321] It is understood that in certain aspects of the present invention, a single component may be replaced with multiple components, and multiple components may be replaced with a single component to provide an element or structure or to perform a given function or functions. Except where such substitutions cannot be used to practice a particular embodiment of the present invention, such substitutions are considered to be within the scope of the present invention.

[0322] The examples presented herein are intended to illustrate potential and special implementations of the present invention. For those skilled in the art, it will be appreciated that these examples are primarily intended to illustrate the purpose of the present invention. Variations of these figures or operations described herein may be present without departing from the spirit of the present invention. For example, in some cases, method steps or operations may be performed or executed in different orders, or multiple operations may be added, deleted or modified.

Claims

1. A method for monitoring intravascular pressure and flow, comprising: measuring a plurality of intravascular blood flow values ​​and a plurality of blood pressure values ​​during each of a plurality of cardiac cycles using one or more sensors; For each cardiac cycle, determining a peak blood flow value among a plurality of intravascular blood flow values ​​in the cardiac cycle; For each cardiac cycle, determining a proximal pressure value and a distal pressure value at the peak blood flow value; calculating a first diagnostic parameter based on the proximal pressure value and the distal pressure value at the peak blood flow value for the plurality of cardiac cycles; as well as The first diagnostic parameter or a second diagnostic parameter determined using the first diagnostic parameter is displayed on a user display for the plurality of cardiac cycles.

2. The method of claim 1, wherein: The first diagnostic parameter is a pressure difference between a proximal pressure value and a distal pressure value.

3. The method of claim 1, wherein: The first diagnostic parameter is a pressure ratio of a distal pressure value to a proximal pressure value.

4. The method according to any one of claims 1 to 3, wherein: The proximal pressure value is a proximal pressure value measured relative to the stenosis.

5. The method according to any one of claims 1 to 3, wherein: The proximal pressure value is the aorta pressure value.

6. The method of claim 1, wherein: The first diagnostic parameter and the second diagnostic parameter are selected from a group consisting of indicators including aortic pressure, distal pressure, flow velocity, maximum flow, minimum flow, relative extreme flow, fractional flow reserve FFR value, coronary blood flow reserve CFR value, coronary flow velocity reserve CFVR value, instantaneous blood flow reserve IFR value, and myocardial resistance IMR value.

7. The method of claim 1, wherein: Measurement of multiple intravascular blood flow values ​​and multiple blood pressure values ​​including: 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 the second resistor disposed in the blood vessel; determining one or more of the blood pressure values ​​using one or more of the first electrical signal and the second electrical signal; determining one or more blood temperature values ​​for the blood vessel using one or more of the first electrical signal and the second electrical signal; and The plurality of intravascular blood flow values ​​for the blood vessel are determined using one or more of the first electrical signal and the second electrical signal.

8. The method of claim 1, wherein: The first diagnostic parameter is an average value of pressure ratios for a plurality of cardiac cycles or an average value of pressure differences for a plurality of cardiac cycles.

9. The method of claim 8, wherein: Calculating a plurality of intravascular blood flow values ​​includes receiving an electrical signal associated with a temperature change of an intravascular thermal convection device that is in thermal communication with the blood vessel, the temperature change associated with a flow change during one or more cardiac cycles.

10. The method of claim 8, further comprising: Calibrate the intravascular data collection system, including: setting a baseline value for a distal pressure signal measured by an intravascular thermal convection device; positioning an intravascular thermal convection device at the delivery catheter opening; prior to advancing the intravascular thermal convection device into the vascular system, setting a baseline value for a temperature signal measured by the intravascular thermal convection device; advancing an intravascular thermal convection device to a position distal to the catheter opening; Make the intravascular thermal convection device pressure signal equal to the aorta pressure signal; calibrating a temperature signal of the intravascular thermal convection device when the intravascular thermal convection device is in a measurement position of interest; and The intravascular thermal convection device is sampled to obtain the intravascular thermal convection device pressure signal value and the thermal convection device temperature value.

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