Method of determining mean transit time using coronary pressure measurement

Abstract

A method includes acquiring, by one or more processing circuits, intravascular data, the intravascular data including a plurality of pressure measurements measured at a location within a blood vessel by an intravascular instrument, and determining, by the one or more processing circuits, a mean transit time parameter based on the plurality of pressure measurements. The mean transit time parameter is indicative of a mean transit time corresponding to a flow rate of blood in the blood vessel.

Description

METHOD OF DETERMINING MEAN TRANSIT TIME USING CORONARY PRESSURE MEASUREMENTCROSS-REFERENCE TO RELATED PATENT APPLICATION

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 523,785, filed June 28, 2023, which is incorporated herein by reference in its entirety.BACKGROUND

[0002] Identifying microvascular resistance in a patient may require one or more data collection systems. For example, a physician may use a pressure wire, angiography, intravascular imaging, etc., to collect data to identify microvascular disease. Angiography may provide an insight as to what is happening within a heart, while a pressure wire may be able to provide certain data measurements within a blood vessel.

[0003] Mean transit time, corresponding to a flow rate of blood in a blood vessel, has traditionally been computed by passing a bolus of chilled saline through a blood vessel and measuring a temperature of the bolus as the bolus passes by a proximal and distal temperature sensor on a pressure wire, which is inserted separate from an optical coherence tomography (“OCT”) catheter. A thermodilution curve may then be plotted based on the temperature of the bolus as it passes the temperature sensors, providing an indication of the flow rate and, therefore, the mean transit time. This process, however, requires additional steps and instruments that can be cumbersome, and is susceptible to operator error due to the dependency on maintaining a certain temperature or temperature range of the bolus.SUMMARY

[0004] One embodiment relates to a method of determining a mean transmit time parameter indicative of a mean transmit time of blood in a blood vessel. The method includes acquiring intravascular data comprising a plurality of pressure measurements measured at a location within the blood vessel by an intravascular instrument during injection of a bolus of fluid, anddetermining, based on the plurality of pressure measurements, the mean transit time parameter.

[0005] Another embodiment relates to a system that includes an intravascular instrument and a data processing subsystem. The intravascular instrument is configured to be inserted into a test target to acquire measurements at a location within a blood vessel and facilitate injecting a bolus of fluid. The data processing subsystem is configured to acquire intravascular data from the intravascular instrument. The intravascular data includes a plurality of pressure measurements. The plurality of pressure measurements provide a raw pressure waveform. The data processing system is further configured to apply a moving average filter to the raw pressure waveform to generate a filtered pressure waveform. The filtered pressure waveform includes a bolus injection portion associated with an injection of the bolus of fluid through the intravascular instrument as the measurements are acquired by the intravascular instrument at the location within the blood vessel. The data processing system is further configured to determine a mean transit time parameter based on the bolus injection portion of the filtered pressure waveform. The mean transit time parameter is indicative of a mean transit time of blood in the blood vessel.

[0006] Still another embodiment relates to a non-transitory computer-readable medium having computer-executable instructions encoded therein. The instructions, when executed by one or more processors, cause the one or more processors to acquire intravascular data including a plurality of pressure measurements measured at a location within a blood vessel by an intravascular instrument during injection of a bolus of fluid, and determine, based on the plurality of pressure measurements, a mean transit time parameter indicative of a mean transit time of blood in the blood vessel. The mean transit time parameter is directly proportional to the mean transit time. The mean transit time parameter is not determined using temperature data.

[0007] This summary is illustrative only and is not intended to be in any way limiting. Other aspects, inventive features, and advantages of the devices or processes described herein will become apparent in the detailed description set forth herein, taken in conjunction with the accompanying figures, wherein like reference numerals refer to like elements.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. l is a schematic diagram of system for determining a mean transit time parameter based on pressure measurements acquired using an intravascular instrument, according to an exemplary embodiment.

[0009] FIG. 2 is a schematic diagram of the system of FIG. 1 where the intravascular instrument includes a first catheter assembly, according to an exemplary embodiment.

[0010] FIG. 3 is a schematic diagram of the system of FIG. 1 where the intravascular instrument includes a second catheter assembly, according to an exemplary embodiment.

[0011] FIG. 4 is a detailed view of the second catheter assembly of FIG. 3, according to an exemplary embodiment.

[0012] FIG. 5 is a detailed view of the intravascular instrument of FIG. 1 including a third catheter assembly, according to an exemplary embodiment.

[0013] FIG. 6 is a detailed view of a first portion of the third catheter assembly of FIG. 5, according to an exemplary embodiment.

[0014] FIG. 7 is a detailed view of a second portion of the third catheter assembly of FIG. 5, according to an exemplary embodiment.

[0015] FIG. 8 is a cross-sectional view of the third catheter assembly of FIG. 5, according to an exemplary embodiment.

[0016] FIG. 9 is a cross-sectional view of the third catheter assembly of FIG. 5, according to another exemplary embodiment.

[0017] FIG. 10 is a detailed view of the intravascular instrument of FIG. 1 including a fourth catheter assembly, according to an exemplary embodiment.

[0018] FIG. 11 is a detailed view of the intravascular instrument of FIG. 1 including a fifth catheter assembly, according to an exemplary embodiment.

[0019] FIG. 12 is a first graph showing a raw pressure waveform and a filtered pressure waveform, according to an exemplary embodiment.

[0020] FIG. 13 is a second graph showing a portion of the filtered pressure waveform extracted from the first graph of FIG. 12 to provide an extracted filtered pressure waveform, according to an exemplary embodiment.

[0021] FIG. 14 is a third graph showing the extracted filtered pressure waveform of the second graph of FIG. 13 zeroed out to provide a zeroed, filtered pressure waveform, according to an exemplary embodiment.

[0022] FIG. 15 is a fourth graph showing the identification of a portion of the zeroed, filtered pressure waveform of the third graph of FIG. 14 that is below zero, according to an exemplary embodiment.

[0023] FIG. 16 is a fifth graph showing the portion of the fourth graph that is below zero of FIG. 15 inverted with an area under the curve identified, according to an exemplary embodiment.

[0024] FIG. 17 is a sixth graph showing the identification of an elapsed time between two points of interest of the zeroed, filtered pressure waveform of the third graph of FIG. 14, according to an exemplary embodiment.

[0025] FIG. 18 is a block diagram of a method for determining a mean transit time parameter based on pressure measurements, according to an exemplary embodiment.DETAILED DESCRIPTION

[0026] Before turning to the figures, which illustrate certain exemplary embodiments in detail, it should be understood that the present disclosure is not limited to the details or methodology set forth in the description or illustrated in the figures. It should also be understood that the terminology used herein is for the purpose of description only and should not be regarded as limiting.

[0027] According to an exemplary embodiment, the present disclosure is generally directed to systems and methods for determining mean transit time (e.g., corresponding to a flow rate of blood in a blood vessel) or a mean transit time parameter associated with or indicative of (e.g., directly proportional to) the mean transit time based on pressure measurements. In some embodiments, an intravascular instrument (e.g., having pressure sensing or collection capabilities, connected to an external device having pressure sensing or collection capabilities, etc.) is used to collect intravascular data of a blood vessel, including the pressure measurements. The intravascular instrument may be or include a pressure wire, a catheter, and / or an intravascular imaging probe.

[0028] By way of example, the intravascular instrument may be inserted into a blood vessel and positioned at a location distal to an area of interest. The intravascular instrument may be used collect the intravascular data including a plurality of pressure measurements when the intravascular instrument is positioned at the location distal to or otherwise proximate the area of interest. In some instances, the intravascular instrument may additionally be used to collect the intravascular data as the intravascular instrument is advanced through the blood vessel to the area of interest. When at the location distal to or otherwise proximate the area of interest, a bolus of fluid (e.g., incompressible fluid, saline, contrast fluid, any suitable hemocompatible fluid, etc.) is injected through the intravascular device to the location distal to or otherwise proximate the area of interest to generate a pressure elevation, which is captured in the pressure measurements. The pressure measurements of the intravascular data may then be processed to determine (e.g., calculate, derive, estimate, etc.) the mean transit time or the mean transit time parameter. In some embodiments, the above process used to determine the mean transit time or the mean transit time parameter is determined using pressure measurements both at rest and at hyperemia.

[0029] The mean transit time or the mean transit time parameter may be used to determine other downstream flow indicators or characteristics such as coronary flow reserve (“CFR”), index of microcirculatory resistance (“IMR”), and / or other diagnostic indices. CFR and / or IMR values may be used to diagnose microvascular disease. According to some examples, pressure measurements and / or any values determined using the pressure measurements may be used to evaluate a lesion within a blood vessel, evaluate potential stent placement,diagnose microvascular disease, etc. Additional factors, combined with CFR and / or IMR determined from the mean transit time or the mean transit time parameter, may be used to identify one or more aspects of microvascular disease within the blood vessel. The additional factors may include, for example, the age, gender, body mass index (“BMI”), medical history, vessel type, vessel condition, treatment history, etc. of the patient. The medical history may include, for example, known heart failure, a previous diagnosis of diabetes, hypertension, etc. Vessel types may include the left anterior descending artery (“LAD”), left circumflex artery (“LCX”), right coronary artery (“RCA”), left marginal artery, diagonal arteries, right marginal artery, etc. Treatment history may include, for example, prior percutaneous coronary intervention (“PCI”), coronary artery bypass graft (“CABG”), etc.

[0030] The systems and methods of the present disclosure may facilitate using a single intravascular instrument to identify and / or diagnose one or more aspects of microvascular disease within a blood vessel. By using a single intravascular instrument, the risk to the patient during the procedure may be decreased as there may be fewer incisions, fewer instruments inserted into the patient, less time in the procedure / operating room, etc. Additionally or alternatively, the systems and methods of the present disclosure may facilitate identifying and / or diagnosing one or more aspects of microvascular disease within a blood vessel without having to rely on temperature measurements or maintaining the temperature of a bolus of fluid within a certain range. Accordingly, by acquiring pressure measurements, rather than relying on temperature measurements, the mean transit time or the mean transit time parameter may be determined without requiring strict adherence to parameters regarding the methodology of injecting the bolus. Accordingly, errors may be reduced that might otherwise result from injection of the bolus at an imperfect time and / or temperature.Additionally, the intravascular instrument may not require temperature sensing capabilities, thereby reducing cost and complexity of the required instrumentation.

[0031] According to the exemplary embodiment shown in FIGS. 1-11, a system, shown intravascular evaluation system 100, includes an insertion and / or sensing tool or device, shown as intravascular instrument 110, and a data collection assembly, shown as data collection subsystem 120. As shown in FIGS. 1-3, the data collection subsystem 120 includes a data receiver and / or transmitter, shown as transceiver 130, a control system orcomputing device, shown as controller 140, and an input / output device, shown as user interface 150.

[0032] According to an exemplary embodiment, the intravascular evaluation system 100 is configured for use in collecting and analyzing intravascular data to facilitate determining various characteristics of a target. More specifically, as shown in FIGS. 1-3, the intravascular instrument 110 is configured to be inserted into and / or engage with the target, shown as test target 160, and positioned at a location distal to or otherwise proximate an area of interest of the test target 160 (e.g., a location in a blood vessel where there is a high calcium or plaque buildup that has restricted blood flow, a possible location for a stent, etc.) to make data measurements to facilitate acquiring intravascular data while being moved to and / or while at the location distal to or otherwise proximate the area of interest of the test target 160. According to an exemplary embodiment, the intravascular instrument 110 includes a pressure sensing device (e.g., a pressure transducer, etc.) or is connectable to an external pressure sensing device to make pressure measurements to facilitate acquiring pressure data. In some embodiments, the intravascular instrument 110 includes or is connectable to other types of sensors to facilitate acquiring other types of intravascular data (e.g., a temperature sensor to acquire temperature data, etc.). A sequence of measurements may be taken before, during, and after the intravascular instrument 110 reaches the area of interest of the test target 160. Each measurement may include a timestamp to indicate when the respective measurement was taken. In some embodiments, the measurements are taken at a predetermined interval of time. By way of example, the intravascular instrument 110 may be configured to acquire pressure measurements and / or temperature measurements every 0.01 seconds as the intravascular instrument 110 is advanced to and / or while at the area of interest.

[0033] According to an exemplary embodiment, the intravascular instrument 110 is configured to transmit the intravascular data to the transceiver 130, and the transceiver 130 is configured to receive and re-transmit the intravascular data to the controller 140. As shown in FIGS. 1 and 3, the intravascular instrument 110 is configured to transmit the intravascular data to the transceiver 130 over a first wired connection 112 using a first wired communication protocol. As shown in FIG. 1, the transceiver 130 is configured to retransmit the intravascular data to the controller 140 over a second wired connection 132 usinga second wired communication protocol. In some embodiments, the first wired communication protocol and the second wired communication protocol are the same. In some embodiments, the first wired communication protocol and the second wired communication protocol are different. As shown in FIG. 2, the intravascular instrument 110 is configured to transmit the intravascular data to the transceiver 130 over a first wireless connection 114 using a first wireless communication protocol (e.g., Bluetooth, Wi-Fi, radio, Zigbee, near field communication (“NFC”), etc.). As shown in FIGS. 2 and 3, the transceiver 130 is configured to re-transmit the intravascular data to the controller 140 over a second wireless connection 134 using a second wireless communication protocol. In some embodiments, the first wireless communication protocol and the second wireless communication protocol are the same. In some embodiments, the first wireless communication protocol and the second wireless communication protocol are different. In some embodiments, the transceiver 130 and the controller 140 of the data collection subsystem 120 are integrated into a single device such that the intravascular instrument 110 communicates directly with the controller 140.

[0034] In some embodiments, the controller 140 is configured to selectively engage, selectively disengage, control, or otherwise communicate with components of the intravascular evaluation system 100. As shown in FIGS. 1-3, the controller 140 is coupled to (e.g., communicably coupled to) other components of the intravascular evaluation system 100 including the intravascular instrument 110 (e.g., directly, indirectly through the transceiver 130, etc.), the transceiver 130, and the user interface 150. By way of example, the controller 140 may send and / or receive signals (e.g., control signals, data signals, etc.) with the intravascular instrument 110 (e.g., directly, indirectly through the transceiver 130, etc.), the transceiver 130, and the user interface 150. According to an exemplary embodiment, the controller 140 is configured to analyze the intravascular data acquired using the intravascular instrument 110 to facilitate determining a mean transit time (e.g., corresponding to a flow rate of blood in the test target 160) or a mean transit time parameter associated with or indicative of (e.g., directly proportional to) the mean transit time (as well as other health or physiological characteristics of the test target 160 or patient associated therewith) based on the intravascular data, and more specifically, based on the pressure data thereof, as described in greater detail herein with respect to FIGS. 12-18.

[0035] The controller 140 may be implemented as a general -purpose processor, an application specific integrated circuit (“ASIC”), one or more field programmable gate arrays (“FPGAs”), a digital-signal-processor (“DSP”), circuits containing one or more processing components, circuitry for supporting a microprocessor, a group of processing components, or other suitable electronic processing components. According to the exemplary embodiment shown in FIG. 1, the controller 140 includes a processing circuit 142, a memory 144, and a communications interface 146. The processing circuit 142 may include an ASIC, one or more FPGAs, a DSP, circuits containing one or more processing components, circuitry for supporting a microprocessor, a group of processing components, or other suitable electronic processing components. In some embodiments, the processing circuit 142 is configured to execute computer code stored in the memory 144 to facilitate the activities described herein. The memory 144 may be any volatile or non-volatile computer-readable storage medium capable of storing data or computer code relating to the activities described herein.According to an exemplary embodiment, the memory 144 includes computer code modules (e.g., executable code, object code, source code, script code, machine code, etc.) configured for execution by the processing circuit 142. The computer code modules may include a plaque (such as calcium plaque) detection module, a display module, a flow rate or mean transit time module, a pressure change module, a temperature change module, a stent detection module, or other detection and display modules. For example, the processing circuit 142 may access the flow rate module for detecting the mean transit time of blood in a blood vessel.

[0036] In some embodiments, the controller 140 may represent a collection of processing devices. In such cases, the processing circuit 142 represents the collective processors of the devices, and the memory 144 represents the collective storage devices of the devices. The communications interface 146 may facilitate communication (e.g., wireless, wired, etc.) with the intravascular instrument 110 (e.g., directly, indirectly through the transceiver 130, etc.), the transceiver 130, and the user interface 150. In some embodiments, the communications interface 146 is configured to perform the functions of the transceiver 130 described herein.

[0037] According to an exemplary embodiment, the user interface 150 includes a display and / or an operator input. The display may be configured to display a graphical user interface(“GUI”), data, graphs, a prognosis, an image, an icon, or still other information or content to an operator. In one embodiment, the display includes a graphical user interface configured to provide information about the test target 160. The operator input may be used by an operator to provide commands to the components of the intravascular evaluation system 100. The operator input may include one or more buttons, knobs, touchscreens, switches, levers, joysticks, a keyboard, a mouse, etc. It should be understood that any type of display and / or input controls may be implemented with the systems and methods described herein. In some embodiments, the controller 140 and the user interface 150 are integrated into a single device (e.g., a desktop computer, a laptop computer, a tablet, a smartphone, etc.).

[0038] By way of example, the display may output data relating to one or more features detected in the test target 160. For example, the output may include, without limitation, pressure data, thermodilution data, aortic and distal pressure, pressure-based indicia of risk posed to stent expansion, flow rate, etc. The display may identify features with a value, text, arrows, color coding, highlighting, contour lines, animation, or other suitable human or machine-readable indicia. For example, the display may output green if the pressure of the blood within a blood vessel is within the given range of pressure measurements and red if the pressure is outside of that range. The range may be programmed by the operator, preset within the processing circuit 142, or configured by artificial intelligence within the processing circuit 142. The display may output a graphic that may be an icon, picture, curve, or other visual image. The display may output an animation that may be a depiction of the blood vessel of the patient with an animation of blood flowing through at a rate of speed corresponding to a determined mean transit time. One or more steps may be performed automatically or without user input to navigate images, input information, select and / or interact with an input, etc. The user interface 150 may be configured to allow for toggling between one or more viewing modes in response to user inputs. For example, a user may be able to toggle between different side branches on the display, such as by selecting a particular side branch and / or by selecting a view associated with the particular side branch. In some examples, the GUI may include a menu. The menu may allow a user to show or hide various features. There may be more than one menu. For example, there may be a menu for selecting blood vessel features to display. Additionally or alternatively, there may be a menufor selecting the target area of the blood vessel where the pressure measurements may be collected.

[0039] According to the exemplary embodiment shown in FIG. 1, the test target 160 is a target of a patient (e.g., a human patient, an animal test subject, etc.), shown as blood vessel 162. The blood vessel 162 may be accessed through the femoral artery or the radial artery, for example. According to the exemplary embodiment shown in FIGS. 2 and 3, the test target 160 is a non-patient target, shown as physiology phantom 164. The physiology phantom 164 may be configured to simulate vascular physiology and be representative of the human vascular system. The physiology phantom 164 may include a combination of hardware and software used to mimic the heart functions and blood flow of a patient. The hardware of the physiology phantom 164 may represent a branch of the coronary artery. The software of the physiology phantom 164 controls the internal hardware, generating conditions found within a coronary artery, such as waveforms similar to the beat of a heart. The physiology phantom 164 may be used for a bench top experiment, for calibration of one or more components of the intravascular evaluation system 100, to train individuals without needing a patient or animal test subject, etc.

[0040] According to various embodiments, the intravascular instrument 110 is or includes one or more of a pressure wire, a guide catheter, a pressure sensing catheter, an OCT probe, a micro-OCT probe, a near infrared spectroscopy (“NIRS”) sensor, or an intravascular ultrasound (“IVUS”) probe. As shown in FIG. 2, the intravascular instrument 110 includes a first assembly, shown as guided pressure wire assembly 200. The guided pressure wire assembly 200 includes (a) a first component or catheter, shown as guide catheter 210, having a first end, shown as distal end 212, and an opposing second end, shown as proximal end 214, and (b) a second component, shown as pressure wire 220, having a first end, shown as distal end 222, and an opposing second end, shown as proximal end 224.

[0041] The guide catheter 210 may be any tube-like delivery apparatus such as any catheter, a guiding sheath, a trocar or a tubular instrument, or the like capable of being used for percutaneous intracoronary procedures. Additionally, the guide catheter 210 may be configured to facilitate measuring aortic pressure of the test target 160. By way of example, the guide catheter 210 may be inserted into the blood vessel 162 (e.g., through the femoralartery, the radial artery, etc.), hyperemia may then be pharmacologically induced (e.g., using adenosine), and the aortic pressure at the opening of the blood vessel 162 may be measured. In some examples, the guide catheter 210 may be connected to a separate transceiver (e.g., similar to the transceiver 130) via a wired or a wireless connection. The separate transceiver (or the transceiver 130) may collect and retransmit the aortic pressure readings to the controller 140 to be used for intravascular calculations.

[0042] As shown in FIG. 2, the pressure wire 220 includes one or more sensors, shown as sensor 226, positioned at or proximate the distal end 222 thereof. According to an exemplary embodiment, the sensor 226 includes a pressure sensor or pressure transducer. In some embodiments, the sensor 226 includes additional sensors positioned therealong (e.g., temperature sensors, at the distal end 222, proximate the distal end 222, spaced a distance from the distal end 222). As shown in FIG. 2, the distal end 222 of the pressure wire 220 is configured to be inserted into the proximal end 214 of the guide catheter 210 to direct the distal end 222 and, therefore, the sensor 226 to the location distal to or otherwise proximate the area of interest of the test target 160 to acquire intravascular measurements (e.g., pressure measurements, temperature measurements, etc.). After the pressure wire 220 is guided to the location distal to or otherwise proximate the area of interest of the test target 160 via the guide catheter 210, a bolus of fluid may be injected into the test target 160 through a purge port of the guided pressure wire assembly 200 such that the bolus flows over / along the pressure wire 220. The sensor 226 of the pressure wire 220 may continue to capture the intravascular measurements as the bolus passes. The bolus of fluid may include an incompressible fluid, saline, contrast fluid, and / or any suitable hemocompatible fluid. According to some examples, because a consistent or particular temperature of the bolus of fluid may not be an important factor for the method of the present disclosure, the temperature of the bolus of fluid does not need to be strictly monitored and managed (e.g., the bolus of fluid may be room temperature, consistent with the body temperature of the patient, etc.).

[0043] As shown in FIG. 2, the pressure wire 220 includes a control device, shown as pressure wire controller 228, positioned at the proximal end 224 thereof. According to an exemplary embodiment, the pressure wire controller 228 is configured to receive information regarding the intravascular measurements (e.g., pressure measurements, temperaturemeasurements, etc.) acquired by the sensor 226 and transmit intravascular data based on the intravascular measurements to the data collection subsystem 120 (e.g., the transceiver 130, the communications interface 146 of the controller 140, etc.) over the first wireless connection 114. In some embodiments, the pressure wire 220 does not include the pressure wire controller 228 and the pressure wire 220 transmits the intravascular data to the data collection subsystem 120 over the first wired connection 112, or the pressure wire controller 228 transmits the intravascular data to the data collection subsystem 120 over the first wired connection 112.

[0044] As shown in FIGS. 3 and 4, the intravascular instrument 110 includes a second assembly, shown as pressure sensing catheter assembly 300. The pressure sensing catheter assembly 300 may be configured to perform similar intravascular measurement functions as the guided pressure wire assembly 200. In various embodiments, the pressure sensing catheter assembly 300 is coupled to or includes an intravascular imaging probe, such as an OCT probe, micro-OCT, NIRS sensor, or an IVUS probe. As shown in FIGS. 3 and 4, the pressure sensing catheter assembly 300 includes (a) a second catheter, shown as catheter 310, having a first end, shown as distal end 312, and an opposing second end, shown as proximal end 314, and (b) an external pressure sensing device, shown as pressure transducer 320.

[0045] As shown in FIG. 4, the catheter 310 defines at least one aperture, shown as aperture 316, positioned proximate the distal end 312 thereof. In some embodiments, the aperture 316 is otherwise positioned along the catheter 310 (e.g., along a mid-section, proximate the proximal end 314, etc. of the catheter 310). In some embodiments, the catheter 310 defines a plurality of apertures 316 (e.g., a plurality of apertures 316 proximate the distal end 312, a plurality of aperture 316 positioned proximate the mid-section, at least one aperture 316 positioned proximate the distal end 312 and at least one aperture 316 proximate the midsection, etc.). As shown in FIG. 3, the catheter 310 defines at least one port, shown as pressure access port 318, positioned proximate the proximal end 314 thereof. The pressure transducer 320 is coupled to the pressure access port 318 and, therefore, in fluid communication with the aperture 316.

[0046] As shown in FIG. 3, the distal end 312 of the catheter 310 is configured to be inserted into the test target 160 and directed to the location distal to or otherwise proximatethe area of interest of the test target 160 to acquire intravascular measurements (e.g., pressure measurements). The catheter 310 may be filled with an incompressible fluid before being inserted into the test target 160. The incompressible fluid may include a contrast fluid, saline, a hemocompatible fluid, or another medium. The pressure transducer 320 may be configured to measure the hydraulic column pressure of the catheter 310 as the catheter 310 is inserted into the test target 160 and the aperture 316 is positioned at the location distal to or otherwise proximate the area of interest of the test target 160. The hydraulic column pressure of the catheter 310 may vary based on the physiology of the test target 160 where the aperture 316 is located (e.g., an increase or decrease in the blood pressure where the blood vessel 162 narrows or widens). As shown in FIG. 3, the pressure transducer 320 is configured to acquire pressure measurements and transmit pressure data based on the pressure measurements to the data collection subsystem 120 over the first wired connection 112. In other embodiment, the pressure transducer 320 is configured to transmit the pressure data to the data collection subsystem 120 over the first wireless connection 114.

[0047] As shown in FIGS. 5-9, the intravascular instrument 110 includes a third assembly, shown as over-the-wire catheter assembly 400. The over-the-wire catheter assembly 400 may be configured to perform similar intravascular measurement functions as the guided pressure wire assembly 200 and / or the pressure sensing catheter assembly 300. As shown in FIGS. 5-9, the over-the-wire catheter assembly 400 includes (a) a first component, shown as guide wire 410, and (b) a second component or third catheter, shown as catheter 420, having a first end, shown as distal end 422, and an opposing second end, shown as proximal end 424. In some embodiments, the over-the-wire catheter assembly 400 includes an external pressure transducer (e.g., similar to the pressure transducer 320). As shown in FIG. 5, the catheter 420 includes a first component, shown as side arm and hypotube 426, at the proximal end 424 of the catheter 420. According to an exemplary embodiment, the side arm and hypotube 426 are configured to facilitate delivering a fluid (e.g., a bolus, a contrast media, saline, a hemocompatible fluid, etc.) to the area of interest of the test target 160.

[0048] As shown in FIGS. 5-9, the catheter 420 includes a second component (e.g., a first polymeric member or tubular component), shown as outer member 428, and a third component (e.g., a second polymeric member or tubular component), shown as inner member430, disposed within the outer member 428 and at the distal end 422 of the catheter 420. The outer member 428 may be coupled (e.g., fixed, bonded, etc.) to the side arm and hypotube 426. The inner member 430 may be joined to the outer member 428 to form a rapid exchange (“RX”) notch. As shown in FIGS. 8 and 9, the inner member 430 defines a passage for delivering the catheter 420 over the guide wire 410 to facilitate proper placement of the catheter 420 within the test target 160. The outer member 428 and the inner member 430 may provide a space therebetween for a column of the fluid provided by the side arm and hypotube 426. In some embodiments, the fluid flows through the space to facilitate delivery of the fluid to the test target 160 (e.g., through an aperture).

[0049] As shown in FIGS. 6, 8, and 9, the outer member 428 defines at least one aperture, shown as aperture 432, positioned proximate the distal end 422 of the catheter 420. The aperture 432 is fluidly connected to the space between the outer member 428 and the inner member 430 and within which the column of the fluid is provided by the side arm and hypotube 426. At the location of the aperture 432, the column of fluid is subjected to the variations of the test target 160, such as variations in blood pressure. According to an exemplary embodiment, a pressure transducer can be coupled to the over-the-wire catheter assembly 400 to acquire pressure measurements regarding the column of fluid based on the variations of the test target interacting with the aperture 432. In some embodiments, the aperture 432 is configured and positioned to be oriented perpendicular to the flow of the blood in the blood vessel 162. Alternatively, the aperture 432 may be configured and positioned to be oriented parallel to the flow. While only one aperture 432 is shown in FIGS. 7 and 8, in some embodiments, a plurality of apertures 432 are defined by the outer member 428. Multiple apertures 432 may facilitate acquiring more accurate pressure measurements. As shown in FIG. 9, a plurality of apertures 432 (e.g., two) are distributed circumferentially around the outer member 428. In some embodiments, the plurality of apertures 432 are additionally or alternatively distributed longitudinally along one or more portions of the outer member 428. The one or more apertures 432 may be formed in the outer member 428 using a heat process. The apertures 432 may be formed with specialized contouring around the edges thereof to prevent fluid turbulence as blood passes over or past the apertures 432. The apertures 432 may have varying sizes between, for example, 0.01 mm2- 4 mm2. In someexamples, the apertures 432 have varying sizes between 0.025 mm2- 2 mm2. The apertures 432 may vary in shape, such as circular, square, triangular, or any polygonal shape.

[0050] As shown in FIG. 10, the intravascular instrument 110 includes a fourth assembly, shown as imaging catheter assembly 500. The imaging catheter assembly 500 may be configured to perform similar intravascular measurement functions as the guided pressure wire assembly 200, the pressure sensing catheter assembly 300, and / or the over-the-wire catheter assembly 400. As shown in FIG. 10, the imaging catheter assembly 500 includes (a) a first component, shown as imaging tool 510, and (b) a second component or fourth catheter, shown as catheter 520, having a first end, shown as distal end 522, and an opposing second end, shown as proximal end 524. According to the exemplary embodiment shown in FIG. 10, the imaging tool 510 is an OCT probe insertable into the catheter 520 and having a fiber optic connector 512, an OCT lens 514, and a radio-opaque marker 516. In other embodiments, the imaging tool 510 is an IVUS probe, NIRS probe, micro-OCT probe, and / or still another imaging tool.

[0051] As shown in FIG. 10, the catheter 520 defines (a) at least one aperture, shown as aperture 526, positioned therealong proximate the distal end 522, (b) a port, shown as purge port 528, positioned therealong proximate the proximal end 524, (c) an entry point, shown as guidewire entry 530, and (d) an exit point, shown as guidewire exit 532. The catheter 520 includes a sealing member, shown as liquid seal 534, positioned rearward of the purge port 528 closer to the proximal end 524 thereof. The purge port 528 may function similar to the pressure access port 318 and facilitate coupling a pressure transducer to the catheter 520.

[0052] According to an exemplary embodiment, the catheter 520 is configured to hold a column of fluid to facilitate pressure measurements at the location proximate the aperture 526. The fluid may be any hemocompatible fluid that will not interfere with the imaging tool 510 (e.g., saline or another suitable medium). The column of fluid may be held in place by the liquid seal 534 and around the imaging tool 510. The purge port 528 may be configure to facilitate pushing a bolus of fluid to the area of interest to properly image the area. The purge port 528 may be used to fill the catheter 520 with the column of fluid for the pressure measurements.

[0053] The aperture 526 may be positioned distal to or otherwise proximate the area of interest, such that the pressure transducer can measure pressure distal to or otherwise proximate the area of interest proximate the aperture 526. The measurement may be initiated when the aperture 526 reaches the area of interest. As the aperture 526 approaches the area of interest, the pressure transducer may, either continuously or at a high rate of acquisition, collect a plurality of distal pressure measurements of the area of interest. The pressure measurements may be taken by the pressure transducer at the aperture 526 within the test target 160 before, during, and after the aperture 526 reaches the area of interest. The pressure measurements can be expressed as a function of time and provides a profile of the pressure across the area of interest.

[0054] As shown in FIG. 11, the intravascular instrument 110 includes a fifth assembly, shown as delivery catheter assembly 600. The delivery catheter assembly 600 may be configured to perform similar intravascular measurement functions as the guided pressure wire assembly 200, the pressure sensing catheter assembly 300, the over-the-wire catheter assembly 400, and / or the imaging catheter assembly 500. As shown in FIG. 11, the delivery catheter assembly 600 includes (a) a first component or fifth catheter, shown as pressure sensing catheter 610, having a first end, shown as distal end 612, and an opposing second end, shown as proximal end 614, and (b) a second component or sixth catheter, shown as delivery catheter 620, having a first end, shown as distal end 622, and an opposing second end, shown as proximal end 624. According to the exemplary embodiment shown in FIG.11, the pressure sensing catheter 610 is similar to the catheter 310 in that the pressure sensing catheter 610 defines (a) at least one aperture, shown as aperture 616, positioned proximate the distal end 612 thereof and (b) at least one port, shown as pressure access port 618, positioned proximate the proximal end 614 thereof. A pressure transducer (e.g., similar to the pressure transducer 320) can be coupled to the pressure access port 618 and, therefore, in fluid communication with the aperture 616. In other embodiments, the pressure sensing catheter 610 is the same or similar to the catheter 420 or the catheter 520.

[0055] As shown in FIG. 11, the delivery catheter 620 includes an inflatable device, shown as balloon 626, positioned proximate the distal end 622 thereof and defines a port, shown as inflation port 628, positioned proximate the proximal end 624 thereof. According to anexemplary embodiment, the inflation port 628 is configured to facilitate inflating and deflating the balloon 626. By way of example, the pressure sensing catheter 610 and the delivery catheter 620 may be advanced into the test target 160 and toward the area of interest simultaneously. The pressure sensing catheter 610 may be configured to hold a column of fluid (e.g., saline, contrast fluid, hemocompatible fluid, etc.) to facilitate measuring the pressure at the aperture 616 with a pressure transducer coupled to the pressure access port 618 as the pressure sensing catheter 610 is advanced through the test target 160. The delivery catheter assembly 600 may facilitate making real time pressure measurements immediately prior to and after an interventional device (e.g., a stent) is placed. For example, a stent may be placed over the balloon 626 and the delivery catheter 620, and advanced to a stent deployment site. Once the stent deployment site is reached, the aperture 616 may be located beyond the site, and the balloon 626 and stent may be within the site. The pressure transducer may collect pre-implantation pressure measurements at the aperture 616. The operator may then inject a solution (e.g., saline) into the inflation port 628 to inflate / expand the balloon 626. The inflation / expansion of the balloon 626 may, thereby, deploy the stent at the stent deployment site within the test target 160 (e.g., the blood vessel 162). The operator may deflate the balloon 626 by removing the solution through the inflation port 628. Once normal flow through the now stented region resumes, the pressure transducer may collect post-implantation pressure measurements at the aperture 616. Such a procedure may allow the operator to verify proper implantation of an interventional device in real time. With these instantaneous pressure measurements, the operator may make decisions as to whether to readjust the interventional device. This may reduce the time of the procedure and, thus, reduce potential health risks to the patient.

[0056] As mentioned above, the controller 140 is configured to analyze the intravascular data acquired using the intravascular instrument 110 to facilitate determining a mean transit time (e.g., corresponding to a flow rate of blood in the test target 160) or a mean transit time parameter associated with or indicative of (e.g., directly proportional to) the mean transit time (as well as other health or physiological characteristics of the test target 160 or patient associated therewith) based on the intravascular data, and more specifically, based on the pressure data thereof. Such analysis is described below with reference to FIGS. 12-18.

[0057] Referring to FIG. 12, as graph 700 is shown with a first waveform, shown as raw pressure waveform 710, and a second waveform, shown as filtered pressure waveform 720. The controller 140 is configured to acquire the pressure measurements from the intravascular instrument 110 and / or the transceiver 130 to generate the raw pressure waveform 710. The raw pressure waveform 710 may, therefore, represent the pressure over time measured by the intravascular instrument 110 while positioned at the location distal to or otherwise proximate the area of interest of the test target 160 (e.g., the blood vessel 162, the physiology phantom 164, etc.). The raw pressure waveform 710 includes a first portion, shown as pre-bolus injection portion 712, a second portion, shown as bolus injection portion 714, and a third portion, shown as post-bolus injection portion 716. The pre-bolus injection portion 712 represents the portion of the raw pressure waveform 710 and, therefore, the pressure measurements acquired via the intravascular instrument 110 prior to the injection of the bolus of fluid with the intravascular instrument 110. The bolus injection portion 714 represents the portion of the raw pressure waveform 710 and, therefore, the pressure measurements acquired via the intravascular instrument 110 when the bolus of fluid is injected with the intravascular instrument 110 and the transient pressure response as a result thereof. The post-bolus injection portion 716 represents the portion of the raw pressure waveform 710 and, therefore, the pressure measurements acquired via the intravascular instrument 110 following the injection of the bolus of fluid with the intravascular instrument 110 and when the transient pressure response to the bolus injection has subsided.

[0058] The controller 140 is configured to apply a moving average filter to the raw pressure waveform 710 to generate the filtered pressure waveform 720. Traditionally, moving average filters are applied over a window of a plurality of cardiac cycles (“CCs”) (e.g., three CCs). However, according to the methods of the present disclosure, the controller 140 is configured to apply the moving average filter based on a single CC (e.g., a single, peak-to-peak CC), as shown in FIG. 12. More specifically, to apply the moving average filter, the controller 140 is configured to (a) determine a length of the single CC based on the raw pressure waveform 710, (b) average the pressure measurements over a first portion of the raw pressure waveform 710 having a window length equivalent to the length of the single CC to determine a point (e.g., an initial or first point) of the filtered pressure waveform 720, (c) move along the raw pressure waveform 710 at an interval of the sample rate of the raw pressure waveform 710,and (d) repeat steps (b) and (c) across the raw pressure waveform 710 to determine each subsequent point of the filtered pressure waveform 720 associated with each subsequent portion of the raw pressure waveform 710. Though the sample rate is 0.01 seconds in this particular example, the sample rate could be other rates (e.g., 0.1 second, 0.001 seconds, or any other sample rate at which the intravascular instrument 110 is capable of acquiring pressure measurements).

[0059] Similar to the raw pressure waveform 710, the filtered pressure waveform 720 generated from the raw pressure waveform 710 includes a first portion, shown as filtered prebolus injection portion 722, a second portion, shown as filtered bolus injection portion 724, and a third portion, shown as filtered post-bolus injection portion 726. The filtered pre-bolus injection portion 722 represents the portion of the filtered pressure waveform 720 prior to the injection of the bolus of fluid with the intravascular instrument 110. The filtered bolus injection portion 724 represents the portion of the filtered pressure waveform 720 when the bolus of fluid is injected with the intravascular instrument 110 and the transient pressure response as a result thereof. The filtered post-bolus injection portion 726 represents the portion of the filtered pressure waveform 720 following the injection of the bolus of fluid with the intravascular instrument 110 and when the transient pressure response to the bolus injection has subsided.

[0060] Referring to FIG. 13, a graph 800 is shown with the filtered bolus injection portion 724 of the filtered pressure waveform 720 extracted from the remainder of the filtered pressure waveform 720. The controller 140 is configured to extract the filtered bolus injection portion 724 from the filtered pressure waveform 720 and identify (e.g., determine, select, etc.) a plurality of points of interest along the filtered bolus injection portion 724. As shown in FIG. 13, the plurality of points of interest include four points of interest, shown as first anchor point 730, second anchor point 732, third anchor point 734, and fourth anchor point 736. In some embodiment, the controller 140 is configured to determine fewer than four anchor points. By way of example, the controller 140 may be configured to determine the first anchor point 730, the second anchor point 732, and fourth anchor point 736, but not the third anchor point 734. In some embodiments, the controller 140 is configured to determine additional anchor points than the four anchor points described herein.

[0061] The controller 140 is configured to determine the first anchor point 730 by evaluating the change in the slope of the filtered bolus injection portion 724 at the beginning or initial portion thereof. More specifically, the controller 140 is configured to take a first derivative of the filtered bolus injection portion 724 and identify when the first derivative is greater than a first, positive derivative threshold, which facilitates identifying when an increase in the slope is greater than a certain amount indicating that the bolus injection has occurred and the transient response thereto has begun. The controller 140 is configured to determine the second anchor point 732 by identifying a maximum inflection point of the filtered bolus injection portion 724. The controller 140 is configured to determine the third anchor point 734 by evaluating the change in the slope of the filtered bolus injection portion 724 following the second anchor point 732. More specifically, the controller 140 is configured to take a second derivative of the filtered bolus injection portion 724 and identify when the absolute value of the second derivative is greater than the absolute value of a second, negative derivative threshold, which facilitates identifying a decrease in the slope of a certain amount indicating that the peak response to the bolus injection is subsiding. The controller 140 may be configured to compare the absolute value of the second derivative to the absolute value of a third, negative derivative threshold that is greater than the absolute value of the second, negative derivative threshold. The third, negative derivative threshold may, therefore, facilitate ignoring the dynamic response and drastic fluctuations immediately following the second anchor point 732. The controller 140 is configured to determine the fourth anchor point 736 by identifying a minimum inflection point of the filtered bolus injection portion 724.

[0062] Referring to FIG. 14, a graph 900 is shown with the filtered bolus injection portion 724 of the filtered pressure waveform 720 from graph 800 “zeroed out” to provide a zeroed, filtered bolus injection portion 728. The controller 140 is configured to reposition the filtered bolus injection portion 724 vertically along the y-axis with that the first anchor point 730 is positioned at zero to provide the zeroed, filtered bolus injection portion 728.

[0063] Referring to FIG. 15, a graph 1000 is shown with the zeroed, filtered bolus injection portion 728 having a reference line, shown as zero line 740, inserted thereon and a subportion, shown as negative portion 750, identified. The zero line 740 may represent a pre-bolus injection value (i.e., the value of the filtered pre-bolus injection portion 722). The controller 140 is configured to identify a first point, shown as start point 752, where the zeroed, filtered bolus injection portion 728 crosses the zero line 740 (or falls below the prebolus injection value) following the first anchor point 730, the second anchor point 732, and the third anchor point 734 to determine the start of the negative portion 750 of the zeroed, filtered bolus injection portion 728. The controller 140 is configured to identify a second point, shown as end point 754, either (a) where the negative portion 750 of the zeroed, filtered bolus injection portion 728 re-crosses the zero line 740 (or is greater than the prebolus injection value) following the start point 752 and the fourth anchor point 136 or (b) if the negative portion 750 does not re-cross the zero line 740 (or if the negative portion 750 is not greater than the pre-bolus injection value at any point following the start point 752), at the point closest to zero line 740 (or the pre-bolus injection value) following the fourth anchor point 136 (e.g., the maximum point or peak, the lowest negative value, etc. following the fourth anchor point 136) to determine the end of the negative portion 750 of the zeroed, filtered bolus injection portion 728.

[0064] Referring to FIG. 16, a graph 1100 is shown with the negative portion 750 of the zeroed, filtered bolus injection portion 728 inverted and an area (a) under the curve between the start point 752 and the end point 754 identified. The controller 140 is configured to invert the negative portion 750 and then determine the area under the curve between the start point 752, the end point 754, and the zero line 740 (e.g., using the Archimedes rectangle method of integration).

[0065] Referring to FIG. 17, a graph 1200 is shown with the zeroed, filtered bolus injection portion 728 having a sampling difference (b) between the second anchor point 732 and the fourth anchor point 736 identified. The controller 140 is configured to determine the sampling difference between the second anchor point 732 and the fourth anchor point 736. The sampling difference may represent the elapsed time or time difference between the second anchor point 732 (i.e., the maximum inflection point of the zeroed, filtered bolus injection portion 728) and the fourth anchor point 736 (i.e., the minimum inflection point of the zeroed, filtered bolus injection portion 728).

[0066] With the area under the curve and the sampling difference determined, the controller 140 is configured to determine a mean transit time parameter that is proportional to the mean transit time corresponding to a flow rate of fluid in the test target 160 (e.g., blood in the blood vessel 162 if the test target 160 is a part of a human patient or an animal test subject, in the physiology phantom 164). The mean transit time parameter may be determined by the controller 140 according to Equation (1).Pmtt — U ' (1)In Equation (1), Pmttis the mean transit time parameter, which is directly proportional to the mean transit time.

[0067] The process performed by the controller 140 to determine the mean transit time parameter, as outlined above with respect to Figures 12-17, can be performed without having to rely on or otherwise evaluate temperature measurements. Also, the process performed by the controller 140 may be performed multiple times to determine the mean transit time parameter both at rest and at hyperemia. Determining the mean transit time parameter at rest may include collecting one or more pressure measurements when the intravascular instrument 110 is held distal to the area of interest in the test target 160 when the test target 160 is in a natural state. For example, the natural state may be the state of the blood vessel 162 without any treatments or medications provided to the human patient or animal test subject.Determining the mean transit time parameter at hyperemia may include collecting one or more pressure measurements when the intravascular instrument 110 is held distal to the area of interest in the test target 160 when the test target 160 is in a hyperemia state. For example, the hyperemia state may be the state of the blood vessel 162 with a treatment or medication provided to the human patient or animal test subject to cause hyperemia (e.g., pharmacologically induced hyperemia).

[0068] The controller 140 may be configured to determined a CFR value for the test target 160 according to Equation (2) and based on the pressure measurements taken both at rest and at hyperemia.In Equation (2), Pmttrestis the mean transit time parameter at rest, arestis the area under the curve of the negative portion 750 of the zeroed, filtered bolus injection portion 728 of the filtered pressure waveform 720 at rest, brestis the sampling rate between the second anchor point 732 and the fourth anchor point 736 of the zeroed, filtered bolus injection portion 728 of the filtered pressure waveform 720 at rest, Pmtthyperemiais the mean transit time parameter at hyperemia, cthyperemta is the area under the curve of the negative portion 750 of the zeroed, filtered bolus injection portion 728 of the filtered pressure waveform 720 at hyperemia, and bhyperemlais the sampling rate between the second anchor point 732 and the fourth anchor point 736 of the zeroed, filtered bolus injection portion 728 of the filtered pressure waveform 720 at hyperemia.

[0069] The controller 140 may be configured to determine the mean transit time at rest and / or at hyperemia based on the mean transit time parameter at rest or at hyperemia, respectively. The controller 140 may be configured to determine the mean transit time at rest according to Equation (3) and the mean transit time at hyperemia according to Equation (4).Tmnrest=Pmttrest'c(3)In Equation (3) and Equation (4), c is a proportionality factor or multiplier. It should be understood that Tmnrestand Tmnhyperemiamay be determined prior to determining the CFR value, and then used in Equation (2) to determine the CFR value. Though, the proportionality factor or multiplier cancels out and, therefore, the proportionality factor is not required to determine the CFR value.

[0070] The controller 140 may be configured to determine a IMR value for the test target 160 according to Equation (5) and based on the mean transit time at hyperemia.In Equation (5), Pdhyperemiais the mean distal pressure during hyperemia. The distal pressure may be determined based on the intravascular data collected by the intravascular instrument 110. For example, the pressure measurements collected by the intravascular instrument 110 when located distal to or otherwise proximate the area of interest may be used as the distal pressure.

[0071] Based on Ohm’s law, a pressure gradient ( P) may be equal to flow rate (Q) multiplied be resistance of the blood vessel 162 ( / ?), as shown in Equation (6).AP = Q ■ R (6)Flow rate may be calculated by theoretical aortic and venous pressures through the resistor model.

[0072] Referring now to FIG. 18, a method 1300 for determining a mean transit time parameter based on pressure measurements (and without using temperature measurements) is shown, according to an exemplary embodiment. The method 1300 may be performed using the intravascular evaluation system 100.

[0073] At step 1302, an intravascular device (e.g., the intravascular instrument 110) is inserted into a test target (e.g., the test target 160) by an operator (e.g., through the femoral artery, the radial artery, etc.) until a portion of the intravascular device is positioned distal to or otherwise proximate an area of interest (e.g., a location within the blood vessel 162, a location of a potential stent implantation, etc.). At step 1304, a data collection system (e.g., the data collection subsystem 120, the controller 140, etc.) is configured to acquire intravascular data with one or more sensors (e.g., the sensor 226, the pressure transducer 320, temperature sensors, pressure sensors, etc.) of the intravascular device. According to an exemplary embodiment, the one or more sensors include at least a pressure sensor or a pressure transducer to acquire pressure measurements that are included with the intravascular data. At step 1306, a bolus of fluid (e.g., saline, contrast fluid, a hemocompatible fluid, an incompressible fluid, etc.) is injected by the operator through the intravascular device. At step 1308, the data collection system is configured to continue acquiring the intravasculardata with the one or more sensors (i.e., the intravascular data is acquired prior to, during, and after injection of the bolus of fluid).

[0074] At step 1310, the data collection system is configured to generate a raw pressure waveform (e.g., the raw pressure waveform 710) based on pressure measurements included with the intravascular data. At step 1312, the data collection system is configured to filter the raw pressure waveform to generate a filtered pressure waveform (e.g., the filtered pressure waveform 720). According to an exemplary embodiment, the data collection system is configured to filter the raw pressure waveform by applying a moving average filter based on a single CC to the raw pressure waveform to generate the filtered pressure waveform. More specifically, the data collection system is configured to apply the moving average filter by (a) determining a length of a single CC based on the raw pressure waveform, (b) averaging the pressure measurements over a first portion of the raw pressure waveform having a window length equivalent to the length of the single CC to determine a point (e.g., an initial or first point) of the filtered pressure waveform, (c) moving along the raw pressure waveform at an interval of the sample rate of the raw pressure waveform, and (d) repeating steps (b) and (c) across the raw pressure waveform to determine each subsequent point of the filtered pressured waveform associated with each subsequent portion of the raw pressure waveform.

[0075] At step 1314, the data collection system is configured to extract a portion of the filtered pressure waveform associated with the injection of the bolus of fluid (e.g., the filtered bolus injection portion 724). At step 1316, the data collection system is configured to identify points of interest positioned along the portion of the filtered pressure waveform. The points of interest include at least a first point (e.g., the first anchor point 730), a second point (e.g., the second anchor point 732), and a third point (e.g., the fourth anchor point 736). In some embodiments, additional points of interest may be identified (e.g., the third anchor point 734) by the data collection system. The data collection system may be configured to determine the first point by evaluating the change in the slope of the portion of the filtered pressure waveform at the beginning or initial portion thereof. More specifically, the data collection system may be configured to take a first derivative of the portion of the filtered pressure waveform and identify when the first derivative is greater than a first, positive derivative threshold, which facilitates identifying when an increase in the slope is greater thana certain amount indicating that the bolus injection has occurred and a transient response thereto has begun. The data collection system may be configured to determine the second point by identifying a maximum inflection point of the portion of the filtered pressure waveform. The data collection system may be configured determine the third point by identifying a minimum inflection point of the portion of the filtered pressure waveform.

[0076] At step 1318, the data collection system is configured to vertically shift or reposition the portion of the filtered pressure waveform such that the first point is positioned at zero along the y-axis (e.g., the zeroed, filtered bolus injection portion 728). At step 1320, the data collection system is configured to determine a sub-portion (e.g., the negative portion 750) of the portion of the filtered pressure waveform that is below a zero line (e.g., the zero line 740) (i.e., negative) and positioned after the first point and the second point along the portion of the filtered pressure waveform. At step 1322, the data collection system is configured to (a) invert the sub-portion, (b) determine a start point (e.g., the start point 752) and an end point (e.g., the end point 754) of the sub-portion, and (c) determine an area under the curve between the zero line, the start point, and the end point (e.g., using the Archimedes rectangle method of integration). The data collection system may be configured to identify the start point where the sub-portion crosses the zero line following the second point. The data collection system may be configured to identify the end point either (a) where the sub-portion re-crosses the zero line following the start point and the third point or (b) if the sub-portion does not re-cross the zero line, at the point closest to zero line following the third point.

[0077] At step 1324, the data collection system is configured to determine a sampling difference (e.g., an elapsed time, a time difference, etc.) between the second point and the third point. The order of (a) step 1320 and step 1322 and (b) step 1324 can be the opposite as shown or performed simultaneously. At step 1326, the data collection system is configured to determine a mean transit time parameter based on the area under the curve and the sampling difference (see, e.g., Equation (1)). At step 1328, if steps 1304-1326 were not performed at hyperemia, but at rest, the operator can then induce hyperemia (step 1330) and then steps 1304-1326 can be repeated. Following steps 1304-1326 being performed at hyperemia, at step 1332, the data collection system is configured to determine characteristicsof the test target (e.g., CFR, IMR, etc.) based on (a) the mean transit time parameters at rest and / or hyperemia and / or (b) other information included with the intravascular data.

[0078] The systems and methods of the present disclosure allow for a simpler procedure allowing for more consistent results and less time spent obtaining the results. Traditional methods use temperature measurements to obtain the mean transit time require the bolus to be chilled to a certain temperature prior to injection into the blood vessel. Such methods require that the operator is highly skilled and works hastily with the chilled fluid before the temperature drops. As a result, such methods can be prone to mistake, potentially calling for multiple tries to collect accurate readings. The method of the present disclosure avoids these issues by allowing the mean transit time to be determined without the use of temperatures, thus reducing procedure time and, therefore, increasing the efficiency and reducing patient discomfort. Moreover, by determining the mean transit time without the use of temperature measurements, the process of determining mean transit time can can more cost effective than other methods that require the use of electrical sensors in the blood vessel to enable temperature measurements.

[0079] According to some examples, at least one of a CFR value or an IMR may be determined based on the determined mean transit time or the determined mean transit time parameter. The CFR value and / or the IMR value may be used in conjunction with one or more patient factors when determining microvascular disease and potential treatments. For example, a physician may consider the patient’s age, gender, BMI, medical history, the vessel type, the vessel condition, prior treatments, etc. in conjunction with the CFR value and / or the IMR value to determine if there is a microvascular disease present and / or a potential treatment.

[0080] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and the age of the patient. For example, the age of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more age specific parameters may be introduced based on training data. In some examples, the age specific parameters may be ranges of age to categorize the patient. The training data may be collected and used as input into a machinelearning model. Based on the one or more age specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0081] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and the gender of the patient. For example, the gender of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. In some examples, the mean transit time, the CFR value, and / or the IMR value may be different based on the patient’s gender. The patent’s gender may be introduced based on training data. The training data may be collected and used as input into a machine learning model. Based on the patient’s gender as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0082] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and the BMI of the patient. For example, the BMI of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more BMI parameters may be introduced based on training data. In some examples, the BMI parameters may be ranges of BMI to categorize the patient. The training data may be collected and used as input into a machine learning model. Based on the one or more BMI parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0083] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and the medical history of the patient. By way of example, medical history, such as known heart failure, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more condition specific parameters may be introduced based on training data. In some examples, the condition specific parameters may be based on the medical history of thepatient. For example, the medical history of the patient may indicate a history of heart failure. The training data may be collected and used as input into a machine learning model. Based on the one or more condition specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0084] As another example, medical history, such as known a previous diagnosis of diabetes, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more condition specific parameters may be introduced based on training data. In some examples, the condition specific parameters may be based on the medical history of the patient. For example, the medical history of the patient may indicate a history of diabetes. The training data may be collected and used as input into a machine learning model. Based on the one or more condition specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0085] As another example, medical history, such as known a previous diagnosis of hypertension, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more condition specific parameters may be introduced based on training data. In some examples, the condition specific parameters may be based on the medical history of the patient. For example, the medical history of the patient may indicate a history of hypertension. The training data may be collected and used as input into a machine learning model. Based on the one or more condition specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0086] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and the vessel type being diagnosed. By way of example, vessel type, such as LAD, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vesselspecific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be LAD. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0087] As another example, vessel type, such as LCX, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vessel specific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be LCX. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0088] As another example, vessel type, such as RCA, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vessel specific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be RCA. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0089] As another example, vessel type, such as the left marginal artery, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vessel specific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be left marginal artery. The training data may be collected and used as input into a machinelearning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0090] As another example, vessel type, such as diagonal arteries, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vessel specific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be diagonal arteries. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0091] As another example, vessel type, such as right marginal artery, of the patient may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more vessel specific parameters may be introduced based on training data. In some examples, the vessel specific parameters may be based on the vessel type. For example, the type may be right marginal artery. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0092] In one example, microvascular resistance may be determined based on the determined mean transit time, the CFR value and / or the IMR value, and patient treatment history. By way of example patient treatment history, such as prior PCI, may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more treatment parameters may be introduced based on training data. In some examples, the treatment parameters may be based on a patient’s treatment history. For example, the patient may have had a prior PCI. Prior PCI may generate microvascular damage and, therefore, may be considered when determining the microvascular resistance of the blood vessel. Thetraining data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0093] As another example, patient treatment history, such as CABG, may be input and processed in conjunction with the CFR value and / or the IMR value to determine the microvascular resistance of a blood vessel. According to some examples, one or more treatment parameters may be introduced based on training data. In some examples, the treatment parameters may be based on a patient’s treatment history. For example, the patient may have had a prior CABG. CABG may alter the cardiac physiology and / or may lead to microvascular alternations and, therefore, may be considered when determining the microvascular resistance of the blood vessel. The training data may be collected and used as input into a machine learning model. Based on the one or more vessel specific parameters as well as the mean transit time, the CFR value, and / or the IMR value, the machine learning model may determine the microvascular resistance of the blood vessel.

[0094] The controller 140 may be configured to control the user interface 150 to display one or more GUIs that provide the graph 700, the graph 800, the graph 900, the graph 1000, the graph 1100, the graph 1200, the mean transit time parameter, the mean transit time, the CFR value, the IMR value, an interface to enter patient treatment history, an interface to enter vessel type, an interface to enter medical history, an interface to enter BMI, an interface to enter gender, an interface to enter age, a prognosis, and / or still other visuals or information.

[0095] As utilized herein, the terms “approximately,” “about,” “substantially”, and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the disclosure as recited in the appended claims.

[0096] It should be noted that the term “exemplary” and variations thereof, as used herein to describe various embodiments, are intended to indicate that such embodiments are possible examples, representations, or illustrations of possible embodiments (and such terms are not intended to connote that such embodiments are necessarily extraordinary or superlative examples).

[0097] The term “coupled” and variations thereof, as used herein, means the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent or fixed) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members coupled directly to each other, with the two members coupled to each other using a separate intervening member and any additional intermediate members coupled with one another, or with the two members coupled to each other using an intervening member that is integrally formed as a single unitary body with one of the two members. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition than the generic definition of “coupled” provided above. Such coupling may be mechanical, electrical, or fluidic.

[0098] References herein to the positions of elements (e.g., “top,” “bottom,” “above,” “below”) are merely used to describe the orientation of various elements in the figures. It should be noted that the orientation of various elements may differ according to other exemplary embodiments, and that such variations are intended to be encompassed by the present disclosure.

[0099] The hardware and data processing components used to implement the various processes, operations, illustrative logics, logical blocks, modules and circuits described in connection with the embodiments disclosed herein may be implemented or performed with a general purpose single- or multi-chip processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions describedherein. A general purpose processor may be a microprocessor, or, any conventional processor, controller, microcontroller, or state machine. A processor also may be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. In some embodiments, particular processes and methods may be performed by circuitry that is specific to a given function. The memory (e.g., memory, memory unit, storage device) may include one or more devices (e.g., RAM, ROM, Flash memory, hard disk storage) for storing data and / or computer code for completing or facilitating the various processes, layers and modules described in the present disclosure. The memory may be or include volatile memory or non-volatile memory, and may include database components, object code components, script components, or any other type of information structure for supporting the various activities and information structures described in the present disclosure. According to an exemplary embodiment, the memory is communicably connected to the processor via a processing circuit and includes computer code for executing (e.g., by the processing circuit or the processor) the one or more processes described herein.

[0100] The present disclosure contemplates methods, systems and program products on any machine-readable media for accomplishing various operations. The embodiments of the present disclosure may be implemented using existing computer processors, or by a special purpose computer processor for an appropriate system, incorporated for this or another purpose, or by a hardwired system. Embodiments within the scope of the present disclosure include program products comprising machine-readable media for carrying or having machine-executable instructions or data structures stored thereon. Such machine-readable media can be any available media that can be accessed by a general purpose or special purpose computer or other machine with a processor. By way of example, such machine- readable media can comprise RAM, ROM, EPROM, EEPROM, or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to carry or store desired program code in the form of machine-executable instructions or data structures and which can be accessed by a general purpose or special purpose computer or other machine with a processor. Combinations of the above are also included within the scope of machine-readable media. Machine-executable instructions include, for example,instructions and data which cause a general purpose computer, special purpose computer, or special purpose processing machines to perform a certain function or group of functions.

[0101] Although the figures and description may illustrate a specific order of method steps, the order of such steps may differ from what is depicted and described, unless specified differently above. Also, two or more steps may be performed concurrently or with partial concurrence, unless specified differently above. Such variation may depend, for example, on the software and hardware systems chosen and on designer choice. All such variations are within the scope of the disclosure. Likewise, software implementations of the described methods could be accomplished with standard programming techniques with rule-based logic and other logic to accomplish the various connection steps, processing steps, comparison steps, and decision steps.

[0102] It is important to note that the construction and arrangement of the intravascular evaluation system 100 and components thereof as shown in the various exemplary embodiments is illustrative only. Additionally, any element disclosed in one embodiment may be incorporated or utilized with any other embodiment disclosed herein.

Claims

CLAIMS:

1. A method of determining a mean transit time parameter indicative of a mean transit time of blood in a blood vessel, the method comprising, by use of one or more processing circuits: acquiring intravascular data comprising a plurality of pressure measurements measured at a location within the blood vessel by an intravascular instrument during injection of a bolus of fluid; and determining, based on the plurality of pressure measurements, the mean transit time parameter.

2. The method of Claim 1, wherein: the mean transit time parameter is directly proportional to the mean transit time.

3. The method of Claim 1, wherein: the mean transit time parameter is not determined using temperature data.

4. The method of Claim 1, further comprising: determining at least one of a coronary flow reserve value or an index of microcirculatory resistance value based on the mean transit time parameter.

5. The method of Claim 4, wherein: the intravascular data includes (a) a first plurality of pressure measurements measured at rest and (b) a second plurality of pressure measurements measured at hyperemia, the step of determining the mean transit time parameter includes (a) determining a first mean transit time parameter based on the first plurality of pressure measurements and (b) determining a second mean transit time parameter based on the second plurality of pressure measurements, and the at least one of the coronary flow reserve value or the index of microcirculatory resistance value are determined based on the first mean transit time parameter and the second mean transit time parameter.

6. The method of Claim 1, wherein: the plurality of pressure measurements provide a raw pressure waveform, and the method further comprises filtering the raw pressure waveform by applying a moving average filter to the raw pressure waveform to generate a filtered pressure waveform, the filtered pressure waveform including a bolus injection portion associated with the injection of the bolus of fluid through the intravascular instrument as the plurality of pressure measurements are measured at the location within the blood vessel by the intravascular instrument, wherein the mean transit time parameter is determined based on the bolus injection portion of the filtered pressure waveform.

7. The method of Claim 6, further comprising: before acquiring the intravascular data, inserting the intravascular instrument into a test target until a portion of the intravascular instrument reaches the location within the blood vessel, and injecting the bolus of fluid through the intravascular instrument; and the step of acquiring the intravascular data comprises acquiring, by a sensor of the intravascular instrument, the plurality of pressure measurements prior to, during, and after the bolus of fluid being injected.

8. The method of Claim 6, wherein: the step of applying the moving average filter to the raw pressure waveform comprises:(a) determining a length of a single cardiac cycle based on the raw pressure waveform,(b) averaging a subset of the plurality of pressure measurements over a first portion of the raw pressure waveform having a window length equivalent to the length of the single cardiac cycle to determine a point of the filtered pressure waveform,(c) moving along the raw pressure waveform at an interval of a sample rate of the raw pressure waveform, and(d) repeating steps (b) and (c) across the raw pressure waveform to determine each subsequent point of the filtered pressure waveform associated with each subsequent portion of the raw pressure waveform.

9. The method of Claim 6, further comprising: determining a first point of interest along the bolus injection portion as a point where the pressure measurements begin to increase from a pre-bolus injection value, due to the injection of the bolus of fluid.

10. The method of Claim 9, further comprising determining, by the one or more processing circuits, a sub-portion of the bolus injection portion that is below the pre-bolus injection value and positioned after the first point of interest along the bolus injection portion.

11. The method of Claim 10, further comprising repositioning, by the one or more processing circuits, the bolus injection portion such that the first point of interest is positioned at zero along a y-axis, wherein the zero line represents the pre-bolus injection value.

12. The method of Claim 10, further comprising: determining an area of the sub-portion.

13. The method of Claim 12, further comprising: inverting the sub-portion, determining a start point of the sub-potion, determining an end point of the sub-portion, and determining the area of the sub-portion that is below the pre-bolus injection value and between the start point and the end point.

14. The method of Claim 13, wherein the step of determining the start point includes identifying where the sub-portion falls below the pre-bolus injection value following the first point of interest, and wherein determining the end point includes identifying either (a) where the sub-portion is greater than the pre-bolus injection value following the start point or (b) if the sub-portion is not greater than the pre-bolus injection value at any point following the start point, at a point closest to the pre-bolus injection value following a minimum point of the sub-portion.

15. The method of Claim 12, further comprising: determining, by the one or more processing circuits, a second point of interest by identifying a maximum value of the bolus injection portion; determining, by the one or more processing circuits, a third point of interest by identifying a minimum value of the bolus injection portion; and determining, by the one or more processing circuits, a sampling difference between the second point of interest and the third point of interest.

16. The method of Claim 15, wherein the mean transit time parameter is determined based on the area and the sampling difference.

17. A system comprising: an intravascular instrument configured to: be inserted into a test target to acquire measurements at a location within a blood vessel; facilitate injecting a bolus of fluid; and a data processing subsystem configured to: acquire intravascular data from the intravascular instrument, the intravascular data including a plurality of pressure measurements, wherein the plurality of pressure measurements provide a raw pressure waveform; apply a moving average filter to the raw pressure waveform to generate a filtered pressure waveform, the filtered pressure waveform including a bolus injection portion associated with an injection of the bolus of fluid through the intravascular instrument as the measurements are acquired by the intravascular instrument at the location within the blood vessel; and determine a mean transit time parameter based on the bolus injection portion of the filtered pressure waveform, the mean transit time parameter indicative of a mean transit time of blood in the blood vessel.

18. The system of Claim 17, wherein the mean transit time parameter is directly proportional to the mean transit time.

19. The system of Claim 17, wherein the mean transit time parameter is not determined using temperature measurements.

20. The system of Claim 17, wherein the data processing subsystem is configured to determine at least one of a coronary flow reserve value or an index of microcirculatory resistance value based on the mean transit time parameter.

21. A non-transitory computer-readable medium having computer-executable instructions encoded therein, the instructions, when executed by one or more processors, cause the one or more processors to: acquire intravascular data comprising a plurality of pressure measurements measured at a location within a blood vessel by an intravascular instrument during injection of a bolus of fluid; and determine, based on the plurality of pressure measurements, a mean transit time parameter indicative of a mean transit time blood in the blood vessel, wherein the mean transit time parameter is directly proportional to the mean transit time, and wherein the mean transit time parameter is not determined using temperature data.

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