Patent Description:
A currently accepted technique for assessing the severity of a stenosis in a blood vessel, including ischemia causing lesions, is fractional flow reserve (FFR). FFR is a calculation of the ratio of a distal pressure measurement (taken on the distal side of the stenosis) relative to a proximal pressure measurement (taken on the proximal side of the stenosis). FFR provides an index of stenosis severity that allows determination as to whether the blockage limits blood flow within the vessel to an extent that treatment is required. The normal value of FFR in a healthy vessel is <NUM>, while values less than about <NUM> are generally deemed significant and require treatment. Common treatment options include angioplasty and stenting.

Coronary blood flow is unique in that it is affected not only by fluctuations in the pressure arising proximally (as in the aorta) but is also simultaneously affected by fluctuations arising distally in the microcirculation. Accordingly, it is not possible to accurately assess the severity of a coronary stenosis by simply measuring the fall in mean or peak pressure across the stenosis because the distal coronary pressure is not purely a residual of the pressure transmitted from the aortic end of the vessel. As a result, for an effective calculation of FFR within the coronary arteries, it is necessary to reduce the vascular resistance within the vessel. Currently, pharmacological hyperemic agents, such as adenosine, are administered to reduce and stabilize the resistance within the coronary arteries. These potent vasodilator agents reduce the dramatic fluctuation in resistance (predominantly by reducing the microcirculation resistance associated with the systolic portion of the heart cycle) to obtain a relatively stable and minimal resistance value.

However, the administration of hyperemic agents is not always possible or advisable. First, the clinical effort of administering hyperemic agents can be significant. In some countries (particularly the United States), hyperemic agents such as adenosine are expensive, and time consuming to obtain when delivered intravenously (IV). In that regard, IV-delivered adenosine is generally mixed on a case-by-case basis in the hospital pharmacy. It can take a significant amount of time and effort to get the adenosine prepared and delivered to the operating area. These logistic hurdles can impact a physician's decision to use FFR. Second, some patients have contraindications to the use of hyperemic agents such as asthma, severe COPD, hypotension, bradycardia, low cardiac ejection fraction, recent myocardial infarction, and/or other factors that prevent the administration of hyperemic agents. Third, many patients find the administration of hyperemic agents to be uncomfortable, which is only compounded by the fact that the hyperemic agent may need to be applied multiple times during the course of a procedure to obtain FFR measurements. Fourth, the administration of a hyperemic agent may also require central venous access ( e.g., a central venous sheath) that might otherwise be avoided. Finally, not all patients respond as expected to hyperemic agents and, in some instances, it is difficult to identify these patients before administration of the hyperemic agent.

<CIT>, according to its abstract, relates to assessing the severity of a blockage in a vessel and, in particular, a stenosis in a blood vessel. In some particular embodiments, the devices, systems, and methods are configured to assess the severity of a stenosis in the coronary arteries without the administration of a hyperemic agent. Further, in some implementations devices, systems, and methods are configured to normalize and/or temporally align pressure measurements from two different pressure sensing instruments. Further still, in some instances devices, systems, and methods are configured to exclude outlier cardiac cycles from calculations utilized to evaluate a vessel, including providing visual indication to a user that the cardiac cycles have been excluded.

Accordingly, there remains a need for improved devices and systems for assessing the severity of a blockage in a vessel and, in particular, a stenosis in a blood vessel. In that regard, there remains a need for improved devices and systems for assessing the severity of a stenosis in the coronary arteries that do not require the administration of hyperemic agents.

The object of the present invention is solved by the subject-matter of the independent claims; further embodiments are incorporated in the dependent claims. Embodiments of the present disclosure are configured to assess the severity of a blockage in a vessel and, in particular, a stenosis in a blood vessel. In some particular embodiments, the devices and systems of the present disclosure are configured to assess the severity of a stenosis in the coronary arteries without the administration of a hyperemic agent. A subset of intravascular pressure measurements obtained during a diagnostic window can be used to calculate a pressure ratio. The diagnostic window can be determined without utilizing electrocardiogram (ECG) data, in some instances. Rather, in such instances, the intravascular pressure measurements can be divided into different time periods, and slopes respectively associated with each time period can be used to identify one or more features of the intravascular pressure measurements, a cardiac cycle of the patient, and/or the diagnostic window.

According to the invention, an intravascular system according to claim <NUM> is provided.

In some embodiments, the processing unit is configured to select a diagnostic window without using electrocardiogram (ECG) data. In some embodiments, the proximal and distal pressure measurements are obtained without administration of a hyperemic agent. In some embodiments, the processing circuit is further configured to calculate the slope over multiple time periods within the cardiac cycle. In some embodiments, a single time period encompasses only a portion of the cardiac cycle. In some embodiments, time periods within the cardiac cycle have the same duration. In some embodiments, the processing circuit is further configured to calculate the slope over multiple time periods of a further cardiac cycle, wherein the time periods of the further cardiac cycle have a different duration than the time periods of the cardiac cycle. In some embodiments, a duration of the time periods is based on a duration of a cardiac cycle. In some embodiments, a duration of the time periods is based on a duration of time periods in one or more previous cardiac cycles. In some embodiments, consecutive time periods at least partially overlap in time. In some embodiments, a starting point of consecutive time periods are offset based on an acquisition rate of the at least one pressure-sensing instrument.

In some embodiments, the processing unit is further configured to identify a sign change of the slope based on calculation of the slope over the plurality of time periods. In some embodiments, the processing unit is further configured to determine, based on the sign change of the slope, at least one of: a minimum pressure measurement, a peak pressure measurement, a beginning of the cardiac cycle, an ending of the cardiac cycle, a beginning of systole, an ending of diastole, a starting point of the diagnostic window, or an ending point of the diagnostic window. In some embodiments, the processing unit is further configured to determine a starting point of the diagnostic window based on the sign change of the slope. In some embodiments, the starting point of the diagnostic window is offset from the sign change of the slope. In some embodiments, the processing unit is further configured to determine a peak pressure measurement based on the sign change of the slope. In some embodiments, the peak pressure measurement is offset from the sign change of the slope. In some embodiments, the processing unit is further configured to determine a starting point of the diagnostic window based on the peak pressure measurement. In some embodiments, the starting point of the diagnostic window is offset from the peak pressure measurement. In some embodiments, the processing unit is further configured to determine a maximum negative slope occurring after the peak pressure measurement. In some embodiments, the processing unit is further configured to determine a starting point of the diagnostic window based on the maximum negative slope. In some embodiments, the starting point of the diagnostic window is offset from the maximum negative slope. In some embodiments, the processing unit is further configured to determine a further sign change of the slope. In some embodiments, the processing unit is further configured to determine a minimum pressure measurement based on the further sign change of the slope. In some embodiments, the minimum pressure measurement is offset from the further sign change of the slope. In some embodiments, the processing unit is further configured to determine an ending point of the diagnostic window based on the minimum pressure measurement. In some embodiments, the ending point of the diagnostic window is offset from the minimum pressure measurement.

In some embodiments, the at least one pressure-sensing instrument comprises: a first pressure-sensing instrument sized and shaped to obtain the proximal pressure measurements while positioned within the vessel at a position proximal of the stenosis of the vessel; and a second pressure-sensing instrument sized and shaped to obtain the distal pressure measurements while positioned within the vessel at a position distal of the stenosis of the vessel. In some embodiments, at least one of the first or second pressure-sensing instruments comprises a catheter, a guide wire, or a guide catheter. In some embodiments, the first pressure-sensing instrument is a catheter and the second pressure-sensing instrument is a guide wire.

In an example, not claimed, a method of evaluating a vessel of a patient is provided. The method includes receiving, at a processing unit in communication with at least one pressure-sensing instrument sized and shaped for introduction into a vessel of the patient, proximal pressure measurements for at least one cardiac cycle of the patient while the at least one pressure-sensing instrument is positioned within the vessel at a position proximal of a stenosis of the vessel; receiving, at the processing unit, distal pressure measurements for the at least one cardiac cycle of the patient while the at least one pressure-sensing instrument is positioned within the vessel at a position distal of the stenosis of the vessel; selecting, using the processing unit, a diagnostic window within a cardiac cycle of the patient by identifying a change in sign of a slope associated with at least one of the proximal pressure measurements or the distal pressure measurements, wherein the diagnostic window encompasses only a portion of the cardiac cycle of the patient; calculating, using the processing unit, a pressure ratio between the distal pressure measurements obtained during the diagnostic window and the proximal pressure measurements obtained during the diagnostic window; and outputting, using the processing unit, the calculated pressure ratio to a display device in communication with the processing unit.

In some embodiments, the selecting a diagnostic window does not include using electrocardiogram (ECG) data. In some embodiments, the obtaining proximal pressure measurements and the obtaining distal pressure measurements do not include administering a hyperemic agent. In some embodiments, the method further includes calculating, using the processing circuit, the slope over multiple time periods within the cardiac cycle. In some embodiments, a single time period encompasses only a portion of the cardiac cycle. In some embodiments, time periods within the cardiac cycle have the same duration. In some embodiments, the method further includes calculating the slope over multiple time periods of a further cardiac cycle, wherein the time periods of the further cardiac cycle have a different duration than the time periods of the cardiac cycle. In some embodiments, a duration of the time periods is based on a duration of a cardiac cycle. In some embodiments, a duration of the time periods is based on a duration of time periods in one or more previous cardiac cycles. In some embodiments, consecutive time periods at least partially overlap in time. In some embodiments, a starting point of consecutive time periods are offset based on an acquisition rate of the at least one pressure-sensing instrument.

In examples, the method further includes identifying, using the processing unit, a sign change of the slope based on the slope calculated over the plurality of time periods. In some examples, the method further includes determining, using the processing unit and based on the sign change of the slope, at least one of: a minimum pressure measurement, a peak pressure measurement, a beginning of the cardiac cycle, an ending of the cardiac cycle, a beginning of systole, an ending of diastole, a starting point of the diagnostic window, or an ending point of the diagnostic window. In some examples, the method further includes determining, using the processing unit, a starting point of the diagnostic window based on the sign change of the slope. In some examples, the starting point of the diagnostic window is offset from the sign change of the slope. In some examples, the method further includes determining, using the processing unit, a peak pressure measurement based on the sign change of the slope. In some examples, the peak pressure measurement is offset from the sign change of the slope. In some examples, the method further includes determining, using the processing unit, a starting point of the diagnostic window based on the peak pressure measurement. In some examples, the starting point of the diagnostic window is offset from the peak pressure measurement. In some examples, the method further includes determining, using the processing unit, a maximum negative slope occurring after the peak pressure measurement. In some examples, the method further includes determining, using the processing unit, a starting point of the diagnostic window based on the maximum negative slope. In some examples, the starting point of the diagnostic window is offset from the maximum negative slope. In some examples, the method further includes determining, using the processing unit, a further sign change of the slope. In some examples, the method further includes determining, using the processing unit, a minimum pressure measurement based on the further sign change of the slope. In some examples, the minimum pressure measurement is offset from the further sign change of the slope. In some examples, the method further includes determining, using the processing unit, an ending point of the diagnostic window based on the minimum pressure measurement. In some examples, the ending point of the diagnostic window is offset from the minimum pressure measurement.

In some examples, the method further includes introducing a first pressure- sensing instrument into the vessel of the patient proximal of the stenosis of the vessel; and introducing a second pressure-sensing instrument into the vessel of the patient distal of the stenosis of the vessel. In some examples, the receiving proximal pressure measurements includes receiving proximal pressure measurements while the first pressure-sensing instrument is positioned within the vessel at a position proximal of the stenosis of the vessel; and the receiving distal pressure measurements includes receiving distal pressure measurements while the second pressure-sensing instrument is positioned within the vessel at a position distal of the stenosis of the vessel. In some examples, the method further includes identifying a treatment option based on the calculated pressure ratio; and performing the identified treatment option.

Referring to <FIG> and <FIG>, shown therein is a vessel <NUM> having a stenosis according to an embodiment of the present disclosure. In that regard, <FIG> is a diagrammatic perspective view of the vessel <NUM>, while <FIG> is a partial cross-sectional perspective view of a portion of the vessel <NUM> taken along section line <NUM>-<NUM> of <FIG>. Referring more specifically to <FIG>, the vessel <NUM> includes a proximal portion <NUM> and a distal portion <NUM>. A lumen <NUM> extends along the length of the vessel <NUM> between the proximal portion <NUM> and the distal portion <NUM>. In that regard, the lumen <NUM> is configured to allow the flow of fluid through the vessel. In some instances, the vessel <NUM> is a systemic blood vessel. In some particular instances, the vessel <NUM> is a coronary artery. In such instances, the lumen <NUM> is configured to facilitate the flow of blood through the vessel <NUM>.

As shown, the vessel <NUM> includes a stenosis <NUM> between the proximal portion <NUM> and the distal portion <NUM>. Stenosis <NUM> is generally representative of any blockage or other structural arrangement that results in a restriction to the flow of fluid through the lumen <NUM> of the vessel <NUM>. Embodiments of the present disclosure are suitable for use in a wide variety of vascular applications, including without limitation coronary, peripheral (including but not limited to lower limb, carotid, and neurovascular), renal, and/or venous. Where the vessel <NUM> is a blood vessel, the stenosis <NUM> may be a result of plaque buildup, including without limitation plaque components such as fibrous, fibro-lipidic (fibro fatty), necrotic core, calcified (dense calcium), blood, fresh thrombus, and mature thrombus. Generally, the composition of the stenosis will depend on the type of vessel being evaluated. In that regard, it is understood that the concepts of the present disclosure are applicable to virtually any type of blockage or other narrowing of a vessel that results in decreased fluid flow.

Referring more particularly to <FIG>, the lumen <NUM> of the vessel <NUM> has a diameter <NUM> proximal of the stenosis <NUM> and a diameter <NUM> distal of the stenosis. In some instances, the diameters <NUM> and <NUM> are substantially equal to one another. In that regard, the diameters <NUM> and <NUM> are intended to represent healthy portions, or at least healthier portions, of the lumen <NUM> in comparison to stenosis <NUM>. Accordingly, these healthier portions of the lumen <NUM> are illustrated as having a substantially constant cylindrical profile and, as a result, the height or width of the lumen has been referred to as a diameter. However, it is understood that in many instances these portions of the lumen <NUM> will also have plaque buildup, a non-symmetric profile, and/or other irregularities, but to a lesser extent than stenosis <NUM> and, therefore, will not have a cylindrical profile. In such instances, the diameters <NUM> and <NUM> are understood to be representative of a relative size or cross-sectional area of the lumen and do not imply a circular cross-sectional profile.

As shown in <FIG>, stenosis <NUM> includes plaque buildup <NUM> that narrows the lumen <NUM> of the vessel <NUM>. In some instances, the plaque buildup <NUM> does not have a uniform or symmetrical profile, making angiographic evaluation of such a stenosis unreliable. In the illustrated embodiment, the plaque buildup <NUM> includes an upper portion <NUM> and an opposing lower portion <NUM>. In that regard, the lower portion <NUM> has an increased thickness relative to the upper portion <NUM> that results in a non-symmetrical and non-uniform profile relative to the portions of the lumen proximal and distal of the stenosis <NUM>. As shown, the plaque buildup <NUM> decreases the available space for fluid to flow through the lumen <NUM>. In particular, the cross-sectional area of the lumen <NUM> is decreased by the plaque buildup <NUM>. At the narrowest point between the upper and lower portions <NUM>, <NUM> the lumen <NUM> has a height <NUM>, which is representative of a reduced size or cross-sectional area relative to the diameters <NUM> and <NUM> proximal and distal of the stenosis <NUM>. Note that the stenosis <NUM>, including plaque buildup <NUM> is exemplary in nature and should be considered limiting in any way. In that regard, it is understood that the stenosis <NUM> has other shapes and/or compositions that limit the flow of fluid through the lumen <NUM> in other instances. While the vessel <NUM> is illustrated in <FIG> and <FIG> as having a single stenosis <NUM> and the description of the embodiments below is primarily made in the context of a single stenosis, it is nevertheless understood that the devices, systems, and methods described herein have similar application for a vessel having multiple stenosis regions.

Referring now to <FIG>, the vessel <NUM> is shown with instruments <NUM> and <NUM> positioned therein according to an embodiment of the present disclosure. In general, instruments <NUM> and <NUM> may be any form of device, instrument, or probe sized and shaped to be positioned within a vessel. In the illustrated embodiment, instrument <NUM> is generally representative of a guide wire, while instrument <NUM> is generally representative of a catheter. In that regard, instrument <NUM> extends through a central lumen of instrument <NUM>. However, in other embodiments, the instruments <NUM> and <NUM> take other forms. In that regard, the instruments <NUM> and <NUM> are of similar form in some embodiments. For example, in some instances, both instruments <NUM> and <NUM> are guide wires. In other instances, both instruments <NUM> and <NUM> are catheters. On the other hand, the instruments <NUM> and <NUM> are of different form in some embodiments, such as the illustrated embodiment, where one of the instruments is a catheter and the other is a guide wire. Further, in some instances, the instruments <NUM> and <NUM> are disposed coaxial with one another, as shown in the illustrated embodiment of <FIG>. In other instances, one of the instruments extends through an off-center lumen of the other instrument. In yet other instances, the instruments <NUM> and <NUM> extend side-by-side. In some particular embodiments, at least one of the instruments is as a rapid-exchange device, such as a rapid-exchange catheter. In such embodiments, the other instrument is a buddy wire or other device configured to facilitate the introduction and removal of the rapid-exchange device. Further still, in other instances, instead of two separate instruments <NUM> and <NUM> a single instrument is utilized. In that regard, the single instrument incorporates aspects of the functionalities (e.g., data acquisition) of both instruments <NUM> and <NUM> in some embodiments.

Instrument <NUM> is configured to obtain diagnostic information about the vessel <NUM>. In that regard, the instrument <NUM> includes one or more sensors, transducers, and/or other monitoring elements configured to obtain the diagnostic information about the vessel. The diagnostic information includes one or more of pressure, flow (velocity), images (including images obtained using ultrasound (e.g., IVUS), OCT, thermal, and/or other imaging techniques), temperature, and/or combinations thereof. The one or more sensors, transducers, and/or other monitoring elements are positioned adjacent a distal portion of the instrument <NUM> in some instances. In that regard, the one or more sensors, transducers, and/or other monitoring elements are positioned less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, and/or less than <NUM> from a distal tip <NUM> of the instrument <NUM> in some instances. In some instances, at least one of the one or more sensors, transducers, and/or other monitoring elements is positioned at the distal tip of the instrument <NUM>.

The instrument <NUM> includes at least one element configured to monitor pressure within the vessel <NUM>. The pressure monitoring element can take the form a piezo-resistive pressure sensor, a piezo-electric pressure sensor, a capacitive pressure sensor, an electromagnetic pressure sensor, a fluid column (the fluid column being in communication with a fluid column sensor that is separate from the instrument and/or positioned at a portion of the instrument proximal of the fluid column), an optical pressure sensor, and/or combinations thereof. In some instances, one or more features of the pressure monitoring element are implemented as a solid-state component manufactured using semiconductor and/or other suitable manufacturing techniques. Examples of commercially available guide wire products that include suitable pressure monitoring elements include, without limitation, the PrimeWire PRESTIGES pressure guide wire, the PrimeWire® pressure guide wire, and the ComboWire® XT pressure and flow guide wire, each available from Volcano Corporation, as well as the PressureWire™ Certus guide wire and the PressureWire™ Aeris guide wire, each available from St. Jude Medical, Inc. Generally, the instrument <NUM> is sized such that it can be positioned through the stenosis <NUM> without significantly impacting fluid flow across the stenosis, which would impact the distal pressure reading. Accordingly, in some instances the instrument <NUM> has an outer diameter of <NUM>" or less. In some embodiments, the instrument <NUM> has an outer diameter of <NUM>" or less.

Instrument <NUM> is also configured to obtain diagnostic information about the vessel <NUM>. In some instances, instrument <NUM> is configured to obtain the same diagnostic information as instrument <NUM>. In other instances, instrument <NUM> is configured to obtain different diagnostic information than instrument <NUM>, which may include additional diagnostic information, less diagnostic information, and/or alternative diagnostic information. The diagnostic information obtained by instrument <NUM> includes one or more of pressure, flow (velocity), images (including images obtained using ultrasound (e.g., IVUS), OCT, thermal, and/or other imaging techniques), temperature, and/or combinations thereof. Instrument <NUM> includes one or more sensors, transducers, and/or other monitoring elements configured to obtain this diagnostic information. In that regard, the one or more sensors, transducers, and/or other monitoring elements are positioned adjacent a distal portion of the instrument <NUM> in some instances. In that regard, the one or more sensors, transducers, and/or other monitoring elements are positioned less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, and/or less than <NUM> from a distal tip <NUM> of the instrument <NUM> in some instances. In some instances, at least one of the one or more sensors, transducers, and/or other monitoring elements is positioned at the distal tip of the instrument <NUM>.

Similar to instrument <NUM>, instrument <NUM> also includes at least one element configured to monitor pressure within the vessel <NUM>. The pressure monitoring element can take the form a piezo-resistive pressure sensor, a piezo-electric pressure sensor, a capacitive pressure sensor, an electromagnetic pressure sensor, a fluid column (the fluid column being in communication with a fluid column sensor that is separate from the instrument and/or positioned at a portion of the instrument proximal of the fluid column), an optical pressure sensor, and/or combinations thereof. In some instances, one or more features of the pressure monitoring element are implemented as a solid-state component manufactured using semiconductor and/or other suitable manufacturing techniques. Millar catheters are utilized in some embodiments. Currently available catheter products suitable for use with one or more of Philips' s Xper Flex Cardio Physiomonitoring System, GE's Mac-Lab XT and XTi hemodynamic recording systems, Siemens's AXIOM Sensis XP VCll, McKesson's Horizon Cardiology Hemo, and Mennen's Horizon XVu Hemodynamic Monitoring System and include pressure monitoring elements can be utilized for instrument <NUM> in some instances.

In accordance with aspects of the present disclosure, at least one of the instruments <NUM> and <NUM> is configured to monitor a pressure within the vessel <NUM> distal of the stenosis <NUM> and at least one of the instruments <NUM> and <NUM> is configured to monitor a pressure within the vessel proximal of the stenosis. In that regard, the instruments <NUM>, <NUM> are sized and shaped to allow positioning of the at least one element configured to monitor pressure within the vessel <NUM> to be positioned proximal and/or distal of the stenosis <NUM> as necessary based on the configuration of the devices. In that regard, <FIG> illustrates a position <NUM> suitable for measuring pressure distal of the stenosis <NUM>. In that regard, the position <NUM> is less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, and/or less than <NUM> from the distal end of the stenosis <NUM> (as shown in <FIG>) in some instances. <FIG> also illustrates a plurality of suitable positions for measuring pressure proximal of the stenosis <NUM>. In that regard, positions <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> each represent a position that is suitable for monitoring the pressure proximal of the stenosis in some instances. In that regard, the positions <NUM>, <NUM>, <NUM>, <NUM>, and <NUM> are positioned at varying distances from the proximal end of the stenosis <NUM> ranging from more than <NUM> down to about <NUM> or less. Generally, the proximal pressure measurement will be spaced from the proximal end of the stenosis. Accordingly, in some instances, the proximal pressure measurement is taken at a distance equal to or greater than an inner diameter of the lumen of the vessel from the proximal end of the stenosis. In the context of coronary artery pressure measurements, the proximal pressure measurement is generally taken at a position proximal of the stenosis and distal of the aorta, within a proximal portion of the vessel. However, in some particular instances of coronary artery pressure measurements, the proximal pressure measurement is taken from a location inside the aorta. In other instances, the proximal pressure measurement is taken at the root or ostium of the coronary artery.

Referring now to <FIG>, shown therein is a system <NUM> according to an embodiment of the present disclosure. In that regard, <FIG> is a diagrammatic, schematic view of the system <NUM>. As shown, the system <NUM> includes an instrument <NUM>. In that regard, in some instances instrument <NUM> is suitable for use as at least one of instruments <NUM> and <NUM> discussed above. Accordingly, in some instances the instrument <NUM> includes features similar to those discussed above with respect to instruments <NUM> and <NUM> in some instances. In the illustrated embodiment, the instrument <NUM> is a guide wire having a distal portion <NUM> and a housing <NUM> positioned adjacent the distal portion. In that regard, the housing <NUM> is spaced approximately <NUM> from a distal tip of the instrument <NUM>. The housing <NUM> is configured to house one or more sensors, transducers, and/or other monitoring elements configured to obtain the diagnostic information about the vessel. In the illustrated embodiment, the housing <NUM> contains at least a pressure sensor configured to monitor a pressure within a lumen in which the instrument <NUM> is positioned. A shaft <NUM> extends proximally from the housing <NUM>. A torque device <NUM> is positioned over and coupled to a proximal portion of the shaft <NUM>. A proximal end portion <NUM> of the instrument <NUM> is coupled to a connector <NUM>. A cable <NUM> extends from connector <NUM> to a connector <NUM>. In some instances, connector <NUM> is configured to be plugged into an interface <NUM>. In that regard, interface <NUM> is a patient interface module (PIM) in some instances. In some
instances, the cable <NUM> is replaced with a wireless connection. In that regard, it is understood that various communication pathways between the instrument <NUM> and the interface <NUM> may be utilized, including physical connections (including electrical, optical, and/or fluid connections), wireless connections, and/or combinations thereof.

The interface <NUM> is communicatively coupled to a computing device <NUM> via a connection <NUM>. Computing device <NUM> is generally representative of any device suitable for performing the processing and analysis techniques discussed within the present disclosure. In some embodiments, the computing device <NUM> includes a processor, random access memory, and a storage medium. In that regard, in some particular instances the computing device <NUM> is programmed to execute steps associated with the data acquisition and analysis described herein. Accordingly, it is understood that any steps related to data acquisition, data processing, instrument control, and/or other processing or control aspects of the present disclosure may be implemented by the computing device using corresponding instructions stored on or in a non-transitory computer readable medium accessible by the computing device. In some instances, the computing device <NUM> is a console device. In some particular instances, the computing device <NUM> is similar to the s5™ Imaging System or the s5i™ Imaging System, each available from Volcano Corporation. In some instances, the computing device <NUM> is portable ( e.g., handheld, on a rolling cart, etc.). Further, it is understood that in some instances the computing device <NUM> comprises a plurality of computing devices. In that regard, it is particularly understood that the different processing and/or control aspects of the present disclosure may be implemented separately or within predefined groupings using a plurality of computing devices. Any divisions and/or combinations of the processing and/or control aspects described below across multiple computing devices are within the scope of the present disclosure.

Together, connector <NUM>, cable <NUM>, connector <NUM>, interface <NUM>, and connection <NUM> facilitate communication between the one or more sensors, transducers, and/or other monitoring elements of the instrument <NUM> and the computing device <NUM>. However, this communication pathway is exemplary in nature and should not be considered limiting in any way. In that regard, it is understood that any communication pathway between the instrument <NUM> and the computing device <NUM> may be utilized, including physical connections (including electrical, optical, and/or fluid connections), wireless connections, and/or combinations thereof. In that regard, it is understood that the connection <NUM> is wireless in some instances. In some instances, the connection <NUM> includes a communication link over a network (e.g., intranet, internet, telecommunications network, and/or other network). In that regard, it is understood that the computing device <NUM> is positioned remote from an operating area where the instrument <NUM> is being used in some instances. Having the connection <NUM> include a connection over a network can facilitate communication between the instrument <NUM> and the remote computing device <NUM> regardless of whether the computing device is in an adjacent room, an adjacent building, or in a different state/country. Further, it is understood that the communication pathway between the instrument <NUM> and the computing device <NUM> is a secure connection in some instances. Further still, it is understood that, in some instances, the data communicated over one or more portions of the communication pathway between the instrument <NUM> and the computing device <NUM> is encrypted.

The system <NUM> also includes an instrument <NUM>. In that regard, in some instances instrument <NUM> is suitable for use as at least one of instruments <NUM> and <NUM> discussed above. Accordingly, in some instances the instrument <NUM> includes features similar to those discussed above with respect to instruments <NUM> and <NUM> in some instances. In the illustrated embodiment, the instrument <NUM> is a catheter-type device. In that regard, the instrument <NUM> includes one or more sensors, transducers, and/or other monitoring elements adjacent a distal portion of the instrument configured to obtain the diagnostic information about the vessel. In the illustrated embodiment, the instrument <NUM> includes a pressure sensor configured to monitor a pressure within a lumen in which the instrument <NUM> is positioned. The instrument <NUM> is in communication with an interface <NUM> via connection <NUM>. In some instances, interface <NUM> is a hemodynamic monitoring system or other control device, such as Siemens AXIOM Sensis, Mennen Horizon XVu, and Philips Xper IM Physiomonitoring <NUM>. In one particular embodiment, instrument <NUM> is a pressure-sensing catheter that includes fluid column extending along its length. In such an embodiment, interface <NUM> includes a hemostasis valve fluidly coupled to the fluid column of the catheter, a manifold fluidly coupled to the hemostasis valve, and tubing extending between the components as necessary to fluidly couple the components. In that regard, the fluid column of the catheter is in fluid communication with a pressure sensor via the valve, manifold, and tubing. In some instances, the pressure sensor is part of interface <NUM>. In other instances, the pressure sensor is a separate component positioned between the instrument <NUM> and the interface <NUM>. The interface <NUM> is communicatively coupled to the computing device <NUM> via a connection <NUM>.

Similar to the connections between instrument <NUM> and the computing device <NUM>, interface <NUM> and connections <NUM> and <NUM> facilitate communication between the one or more sensors, transducers, and/or other monitoring elements of the instrument <NUM> and the computing device <NUM>. However, this communication pathway is exemplary in nature and should not be considered limiting in any way. In that regard, it is understood that any communication pathway between the instrument <NUM> and the computing device <NUM> may be utilized, including physical connections (including electrical, optical, and/or fluid connections), wireless connections, and/or combinations thereof. In that regard, it is understood that the connection <NUM> is wireless in some instances. In some instances, the connection <NUM> includes a communication link over a network ( e.g., intranet, internet, telecommunications network, and/or other network). In that regard, it is understood that the computing device <NUM> is positioned remote from an operating area where the instrument <NUM> is being used in some instances. Having the connection <NUM> include a connection over a network can facilitate communication between the instrument <NUM> and the remote computing device <NUM> regardless of whether the computing device is in an adjacent room, an adjacent building, or in a different state/country. Further, it is understood that the communication pathway between the instrument <NUM> and the computing device <NUM> is a secure connection in some instances. Further still, it is understood that, in some instances, the data communicated over one or more portions of the communication pathway between the instrument <NUM> and the computing device <NUM> is encrypted.

It is understood that one or more components of the system <NUM> are not included, are implemented in a different arrangement/order, and/or are replaced with an alternative device/mechanism in other embodiments of the present disclosure. For example, in some instances, the system <NUM> does not include interface <NUM> and/or interface <NUM>. In such instances, the connector <NUM> (or other similar connector in communication with instrument <NUM> or instrument <NUM>) may plug into a port associated with computing device <NUM>. Alternatively, the instruments <NUM>, <NUM> may communicate wirelessly with the computing device <NUM>. Generally speaking, the communication pathway between either or both of the instruments <NUM>, <NUM> and the computing device <NUM> may have no intermediate nodes (i.e., a direct connection), one intermediate node between the instrument and the computing device, or a plurality of intermediate nodes between the instrument and the computing device.

In some embodiments of the present disclose, a ratio of intravascular pressure measurements obtained during a portion of the heartbeat cycle or diagnostic window is calculated. For example, <FIG> includes graphical representation <NUM> having a plot <NUM> representative of pressure (measured in mmHg) within a vessel over the time period of one cardiac cycle and a plot <NUM> representative of velocity (measured in mis) of a fluid within the vessel over the same cardiac cycle. <FIG> is annotated to identify a diagnostic window <NUM>. The diagnostic window identifies a portion of the heartbeat cycle of the patient where the resistance (e.g., pressure divided by velocity) within vasculature is reduced without the use of a hyperemic agent or other stressing technique. That is, the diagnostic window <NUM> corresponds to a portion of the heartbeat cycle of a resting patient that has a naturally reduced and relatively constant resistance.

The portion of the heartbeat cycle coinciding with the diagnostic window <NUM> can be utilized to evaluate a stenosis of the vessel of a patient without the use of a hyperemic agent or other stressing of the patient's heart. In particular, the pressure ratio (e.g., distal pressure divided by proximal pressure) across the stenosis is calculated for the time period corresponding to the diagnostic window <NUM> for one or more heartbeats. The calculated pressure ratio is an average over the diagnostic window in some instances. By comparing the calculated pressure ratio to a threshold or predetermined value, a physician or other treating medical personnel can determine what, if any, treatment should be administered. In that regard, in some instances, a calculated pressure ratio above a threshold value (e.g., <NUM> on a scale of <NUM> to <NUM>) is indicative of a first treatment mode ( e.g., no treatment, drug therapy, etc.), while a calculated pressure ratio below the threshold value is indicative of a second, more invasive treatment mode (e.g., angioplasty, stent, etc.). In some instances, the threshold value is a fixed, preset value. In other instances, the threshold value is selected for a particular patient and/or a particular stenosis of a patient. In that regard, the threshold value for a particular patient may be based on one or more of empirical data, patient characteristics, patient history, physician preference, available treatment options, and/or other parameters. Various aspects of the diagnostic window, including identification of the diagnostic window, features of the diagnostic window, etc., are described in <CIT> (published as <CIT>).

Referring now to <FIG>, shown therein are various graphical representations of techniques for determining start and/or end points for a diagnostic window in conjunction with an ECG signal in accordance with the present disclosure. The graphical representation <NUM> of <FIG> illustrates a proximal pressure waveform <NUM>, a distal pressure waveform <NUM>, and an associated ECG waveform <NUM>. The proximal pressure waveform <NUM> and distal pressure waveform <NUM> are representative of proximal and distal pressure measurements obtained within the vasculature. The ECG waveform <NUM> is representative of an ECG signal of the patient obtained at the same time as the proximal and distal pressure measurements are obtained. In that regard, the waveforms <NUM>, <NUM>, <NUM> in <FIG> are arranged to show how the illustrated physiological attributes are generally aligned in time.

Referring again to <FIG>, a computing device can identify feature(s) of a diagnostic window, pressure waveform(s) <NUM>, <NUM>, and/or the patient's cardiac cycle based on the ECG waveform <NUM>. For example, using the peak of the R-wave in the ECG waveform <NUM>, the computing device can identify a minimum pressure value or valley <NUM>, <NUM> for each cardiac cycle. In particular, the peak of the R-wave in the ECG waveform <NUM> occurs at a time <NUM> that corresponds to the minimum pressure value <NUM> in the distal pressure waveform <NUM>. The next peak of the R-wave in the ECG waveform <NUM> (for the next cardiac cycle) occurs at a time <NUM> that corresponds to the minimum pressure value <NUM> in the distal pressure waveform <NUM>. In that regard, the minimum pressure value <NUM> corresponds to a cardiac cycle (n), and the minimum pressure value <NUM> corresponds to a next cardiac cycle (n+ <NUM>). The time <NUM> corresponds to the beginning of the cardiac cycle (n) and/or the beginning of systole (n). The time <NUM> corresponds to the end of the cardiac cycle (n), beginning of the next cardiac cycle (n+ <NUM>), the end of diastole (n), and/or the beginning of systole (n+ <NUM>). While the distal pressure waveform <NUM> is specifically mentioned in this discussion, it is understood that the proximal pressure waveform <NUM> can be similarly utilized. Generally, at least one identifiable feature of the ECG signal (including without limitation, the start of a P-wave, the peak of a P-wave, the end of a P-wave, a PR interval, a PR segment, the beginning of a QRS complex, the start of an R-wave, the peak of an R-wave, the end of an R-wave, the end of a QRS complex (J-point), an ST segment, the start of a T-wave, the peak of a T-wave, and the end of a T-wave) can utilized to select that starting point and/or ending point of the diagnostic window, identify features of the proximal or distal pressure waveforms <NUM>, <NUM>, etc., as described for example, in <CIT> (published as <CIT>).

Referring now to <FIG>, shown therein is a graphical representation <NUM> of selecting a diagnostic window based on the feature(s) of the pressure waveform(s) identified using the ECG signal. In some instances, the starting point <NUM> and/or ending point <NUM> of the diagnostic window <NUM> is determined by adding or subtracting a fixed amount of time <NUM>, <NUM> to an identifiable feature of the ECG signal. In that regard, the fixed amount time <NUM>, <NUM> can be a percentage of the cardiac cycle <NUM> in some instances. In that regard, the diagnostic window or wave-free period <NUM> can be identified based on the minimum pressure values <NUM>, <NUM>. For example, the time period <NUM> between the minimum pressure values <NUM>, <NUM> corresponds to the duration of a cardiac cycle. A computing device can select a beginning point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the total cardiac cycle time <NUM> from the time <NUM>. That is, the beginning point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the minimum pressure value <NUM>. A computing device can select an ending point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the total cardiac cycle time <NUM> from the time <NUM>. That is, the ending point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the next minimum pressure value <NUM>. One, the other, or both of the periods <NUM>, <NUM> can be described as a percentage of the total cardiac cycle time <NUM>, including values between about <NUM>% and about <NUM>%, between about <NUM>% and about <NUM>%, between about <NUM>% and <NUM>%, such as <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, and/or other suitable values both larger and smaller.

Referring now to <FIG>, shown therein is a graphical representation <NUM> of selecting a diagnostic window based on the feature(s) of the pressure waveform(s) identified using the ECG signal, according to another embodiment of the present disclosure. In that regard, the diagnostic window or wave-free period <NUM> can be identified based on the minimum pressure values <NUM>, <NUM>. Starting from the minimum pressure value <NUM>, a computing device can identify a peak pressure value <NUM> in the distal pressure waveform <NUM>. The computing device can identify a maximum negative/down slope value <NUM> that occurs after the peak pressure value <NUM>. The maximum negative/down slope value <NUM> identifies when the pressure waveform <NUM> decreases at the fastest rate. The diagnostic window <NUM> can be selected within the period <NUM> between the maximum down slope value <NUM> and the next minimum pressure value <NUM>. In that regard, the computing device can select a beginning point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the period <NUM> from the time <NUM>. That is, the beginning point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the maximum down slope value <NUM>. A computing device can select an ending point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the period <NUM> from the time <NUM>. That is, the ending point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the next minimum pressure value <NUM>. One, the other, or both of the periods <NUM>, <NUM> can be described as a percentage of the period <NUM>, including values between about <NUM>% and about <NUM>%, between about <NUM>% and about <NUM>%, between about <NUM>% and <NUM>%, such as <NUM>%, <NUM>%, <NUM>%, and/or other suitable values both larger and smaller. For example, the period <NUM> can be <NUM>% of the period <NUM>, and the period <NUM> can be <NUM>% of the period <NUM>.

Referring now to <FIG>, shown therein are various graphical representations of techniques for determining start and/or end points for a diagnostic window. In particular, the algorithm described in the <FIG> uses a segment-by-segment analysis of the pressure waveform(s) to identify feature(s) of the cardiac cycle (e.g., the beginning/ending of a cardiac cycle) and/or the pressure waveform(s) themselves (e.g., a minimum pressure value, a peak pressure value, etc.). The diagnostic window is then selected based on the identified feature(s). In that regard, an ECG signal is not used to identify the diagnostic window, a feature of the pressure waveform(s), and/or a feature of the cardiac cycle. Thus, any discomfort experienced by the patient associated with obtaining the ECG signal can be advantageously avoided.

Referring now to <FIG>, shown therein is a graphical representation <NUM> of a distal pressure waveform <NUM>. As described herein, the waveform <NUM> is a based on distal pressure measurements obtained by an intravascular device disposed within vasculature. While a distal pressure waveform is specifically referenced in this discussion, it is understood that a proximal pressure waveform can be similarly utilized. Additionally, while the waveforms in <FIG> and elsewhere are shown as smooth, it is understood that the waveforms comprise discrete pressure measurement s).

A segment 740a of the pressure waveform <NUM> is indicated in <FIG>. The segment 740a identifies a portion of the pressure waveform <NUM>, a subset of the pressure measurements associated with the pressure waveform <NUM>, and/or a time period associated with the pressure waveform <NUM>. As described herein, a period-by-period or segment-by-segment analysis is used to identify features of the cardiac cycle and/or the pressure waveform itself. In some instances, time period, period, and/or segment may be used interchangeably in the discussion herein. The time period or segment 740a has a segment width (SW). That is, the pressure measurements associated with the segment 740a are obtained over the given time. For example, the width or duration of the segment 740a can be less than a cardiac cycle duration, encompassing only a portion of the cardiac cycle. In various embodiments, the duration of the segment 740a compared to the cardiac cycle duration is between approximately <NUM>% and approximately <NUM>%, approximately <NUM>% and approximately <NUM>%, approximately <NUM>% and approximately <NUM>%, including values such as <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, and/or other suitable values both larger and smaller. In some instances, a cardiac cycle duration can be approximately <NUM> second. For example, the duration of the segment 740a can be between approximately <NUM> seconds and approximately <NUM> seconds, approximately <NUM> seconds and approximately <NUM> seconds, approximately <NUM> seconds and approximately <NUM> seconds, including values such as <NUM> seconds, <NUM> seconds, <NUM> seconds, <NUM> seconds, <NUM> seconds, and/or other suitable values both larger and smaller. In some embodiments, the width or duration of the segment 740a varies for each cardiac cycle. For example, time periods associated with different cardiac cycles have different durations. In that regard, the duration of the segment 740a can be adjusted manually by a user or automatically by a computing device. For example, the duration of the segment 740a can be based on the cardiac cycle duration of the cardiac cycle. In that regard, the cardiac cycle duration can be described as the duration between consecutive peak pressure values, consecutive minimum pressure values, etc. For example, the duration of the segment 740a of a cardiac cycle (n) can be based on the duration of one or more earlier cardiac cycles (n-<NUM>, n-<NUM>, etc.) such that the duration is adaptive to a patient's heart rhythm. In some embodiments, a duration of the time periods is based on a duration of time periods in one or more previous cardiac cycles. For example, the duration of the segment 740a can an average of earlier segment durations. That is, the duration of segment 740a can be the average of multiple, prior segment durations. The number of prior segments considered can be variable, adjustable manually by a user, and/or adjustable automatically be a computing device. In some embodiments, the width or duration of the segment 740a can be defined by a quantity of pressure measurements obtained during the segment. In some embodiments, the duration of the segment 740a is bounded by a maximum duration and a minimum duration. In some embodiments, the duration of the segment 740a (e.g., relative to a cardiac cycle) is optimized during manufacture of an intravascular system, while in other embodiments, the duration of the segment can be adjusted prior to, during, and/or after an intravascular procedure.

Referring now to <FIG>, shown therein is a graphical representation <NUM> illustrating a period-by-period analysis of the pressure waveform <NUM>. Also shown is a segment slope waveform <NUM> illustrating a slope of the pressure waveform <NUM> associated with each segment. According to an aspect of the present disclosure, a period-by-period analysis of the slope of the pressure waveform <NUM> is used to identify feature(s) of the cardiac cycle (e.g., the beginning/ending of a cardiac cycle) and/or the pressure waveform(s) itself (e.g., a minimum pressure value, a peak pressure value, etc.). Generally, specific patterns exist within arterial blood pressure waveforms. The patterns, such as maxima (peaks) and minima (valleys) of the pressure waveforms, can be used to identify the cardiac cycle and the wave-free diagnostic period within the cardiac cycle. In the case of healthy vasculature with a regular cardiac cycle, there are minimal artifacts in the pressure signals. Thus, the peaks and valleys of the pressure waveforms can be detected by simply finding the minimum and the maximum values, without the aid of massive filtering processes. However, the pressure signals from diseased hearts are typically distorted by abnormal heart operations (e.g., arrhythmia, premature ventricular contraction, etc.) and/or motion artifacts resulting from pressure measurement (e.g., pullback of the pressure-sensing intravascular device). Therefore, complicated filtering procedures are typically needed to remove those corruptions and to have clean pressure signals from which to visualize peaks and valleys clearly. In that regard, the algorithm described herein advantageously provides for robust identification of features of the cardiac cycle and/or pressure waveform, even in diseased vasculature and without the need for extensive signal filtering hardware or software.

<FIG> illustrates a plurality of period segments 740a, 740b, 740c. It is understood the segments 740a-740c are only a portion of the total number of segments used to analyze pressure waveform <NUM>. In some embodiments, the width or duration of each segment 740a- 740c is the same for a given cardiac cycle. For example, time periods associated with a single cardiac cycle have the same duration. In some embodiments, the each of the segments 740a-740c are consecutive or adjacent in time. For example, a beginning point, midpoint, and/or ending point of the segments 740a, 740b, 740c can be adjacent in time. For example, every subsequent pressure sample may define the beginning of a different segment. Each of the segments 740a-740c can be defined by a starting time, ending time, and/or midpoint time. Consecutive segments can be separated by a period between about <NUM> seconds and about <NUM> seconds, about <NUM> seconds and <NUM> seconds, and/other suitable values both larger and smaller, including the time between consecutive pressure measurements. In some embodiments, a starting point of consecutive time periods or segments can be offset based on an acquisition rate of an intravascular pressure-sensing device. For example, data can be acquired from the pressure-sensing instrument for <NUM> every <NUM> and/or other suitable rates. Consecutive time periods can be offset by about <NUM> in such embodiments and/or other suitable times in different embodiments. In some embodiments, the segments 740a-740c are overlapping in time. In that regard, the segments 740a-740c can overlap by any suitable amount of time. In some embodiments, the time period associated with the overlap can be adjusted manually by a user or automatically by a computing device. In some embodiments, the overlap can be defined by a quantity of pressure measurements. It is understood that the overlap between segments 740a-740c illustrated in <FIG> is exemplary, and other overlap times, both larger and smaller, are contemplated.

The segment slope waveform <NUM> is a plot of the slope of each time period or segment (such as segments 740a-740c) of the pressure waveform <NUM>. In some embodiments, a computing device can calculate the slope of the pressure waveform <NUM> calculated at each pressure sample. The slope may be an average slope of the segment, an instantaneous slope of the segment (e.g., at the beginning point, a midpoint, and/or the ending point), and/or other suitable quantity. For the example, the slope may be calculated as a change/difference in two pressure measurements divided by the change/difference in time between the two pressure measurements. In that regard, with a sufficiently wide segment width and with an average slope calculated across the entire duration of the segment, the slope is advantageously less sensitive to the distorted high and low frequency peaks resulting from abnormal vasculature conditions or motion artifacts from pressure measurements. In some embodiments, the sample location where the average slope is calculated is at or near the sample in the middle of the segment. For example, the average slope, at the midpoint of the segment, may be calculated as the
change/difference in the pressure measurement between the starting point and the ending point of the segment divided by the change/difference in time between the starting and ending points. As illustrated in <FIG>, the value of the segment slope waveform <NUM> changes along the pressure waveform <NUM> as, e.g., the average slope of each segment of the pressure waveform <NUM> is determined. In some instances, the sign or polarity of the segment slope waveform <NUM> switches between positive and negative (or vice versa).

The slope of multiple time periods or segments 745a, 745b, 745c, 745d, 745e, 745f is also illustrated in <FIG>. In that regard, each of the segments 745a-745f is represented by a linear segment spanning its associated pressure measurements on the pressure waveform <NUM>. That is, the length of the linear segments can correspond to the duration or width of the segments 745a-745f. As described with respect to segments 740a-740c, for a given cardiac cycle, the segments 745a-745f have equal width or span the same amount of time. The linear segments are also shown as angled to match the average slope associated with the segments 745a-745f. For example, the segment 745a spans a portion of the pressure waveform <NUM> having a generally positive slope. Correspondingly, the linear segment for segment 745a is shown having a generally positive slope. Segments 745b-745f variously span different portions the pressure waveform <NUM> that having positive slope, zero slope, and/or negative slope. As the influence of the zero slope or negative slope portions increases (towards the right of pressure waveform <NUM>), the linear segments are illustrated as having less positive slope than segment 745a. For example, segments 745b, 745c span portions of the pressure waveform <NUM> having zero slope and negative slope. Thus, the linear segment associated with segments 745b, 745c have a less positive slope, compared to the linear segment associated with segment 745a, which only spans portions of the pressure waveform <NUM> having positive slope. Segment 745d spans portions of the pressure waveform <NUM> with an average slope of zero. Thus, the linear segment is illustrated as having zero slope. Segments 745e and 745f span relatively larger portions of the pressure waveform <NUM> with negative slope, and, thus, the corresponding linear segments have negative slopes. The corresponding slope values are plotted in the segment slope waveform <NUM>. Generally, the slope of the segments 745a-745f changes in the direction indicated by arrow <NUM>. The portion of the pressure waveform <NUM> spanned by the segments 745a-745f includes a change in slope sign. This is illustrated by the linear segments for segments 745a-745f changing slope from positive to negative. Likewise, the segment slope waveform <NUM> corresponding to the area of segments 745a-745f starts positive, crosses the zero line, and becomes negative.

Referring now to <FIG>, shown therein is a graphical representation <NUM> including the pressure waveform <NUM> and segment slope waveform <NUM>, similar to that of graphical representation <NUM> (<FIG>). Graphical representation <NUM> also includes a segment slope waveform <NUM> that is offset from the segment slope waveform <NUM> by a period <NUM>. In that regard, the period <NUM> can correspond to a calculation delay in embodiments in which the segment slope is calculated around the pressure sample at or near middle of the segment 740a. Thus, in such embodiments, the first segment slope is calculated only after approximately half of the duration of the segment 740a. In general, the period <NUM> can be described as a multiple of the segment width (a*SW). In that regard, the multiple can be greater than, equal to, or less than one (a> <NUM>, a = <NUM>, or a < <NUM>) in different embodiments. For example, the multiple (a) can be between about <NUM> and about <NUM>, about <NUM> and about <NUM>, about <NUM> and about <NUM>, including values such as <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and/or other suitable values both larger and smaller. <FIG> illustrates that values of the segment slope waveform <NUM> can be shifted to account for the calculation delay. For example, the slope 744a is shifted in the direction <NUM> by a time equaling the period <NUM>, which yields the slope 744b. The shifted segment slope waveform <NUM> results when all values for the segment slope waveform <NUM> are similarly modified. In some embodiments, the algorithm described herein that identifies features of the diagnostic window, cardiac cycle, and/or the pressure waveform utilizes the shifted waveform <NUM>.

Referring now to <FIG>, shown therein a graphical representation <NUM> including the pressure waveform <NUM> and the segment slope waveform <NUM>. Also illustrated is a feature plot <NUM>, identifying when minima (valley) and maxima (peak) of the pressure waveform <NUM> occur. In that regard, the waveforms <NUM>, <NUM>, <NUM> in <FIG> and elsewhere are arranged show alignment in time or the simultaneous occurrence of one or more physiological attributes. According to aspects of the present disclosure, the minima <NUM>, <NUM> and maxima <NUM>, <NUM> of the pressure waveform <NUM> are identified based on when the sign changes in segment slope waveform <NUM>. The minima <NUM> (n-<NUM>) of the pressure waveform <NUM> can correspond to the beginning of the cardiac cycle (n-<NUM>) and/or the beginning of systole (n-<NUM>). The next minima <NUM> (n) can correspond to the end of the cardiac cycle (n-<NUM>), the end of diastole (n-<NUM>), the beginning of the cardiac cycle (n), and/or the beginning of systole (n). Thus, the features of the cardiac cycle can also be identified based on when sign changes in segment slope waveform <NUM>. Correspondingly, the diagnostic window (e.g., the beginning, the ending, etc.) can be selected based on when the sign changes in segment slope waveform <NUM>.

The sign of the segment slope waveform <NUM> changes at times <NUM>, <NUM>, <NUM>, <NUM>. In particular, the sign of the segment slope waveform <NUM> changes from positive to negative at times <NUM> and <NUM>. The locations <NUM>, <NUM> in segment slope waveform <NUM> correspond to these positive to negative sign changes. The minima <NUM>, <NUM> of the pressure waveform <NUM> can be identified based on the location the sign of the segment slope waveform <NUM> changes from positive to negative. For example, the minimum <NUM> can occur at a time <NUM>, prior to the time <NUM> associated with the sign change <NUM>. In an embodiment, the time <NUM> occurs at half of the segment width before the time <NUM>. Thus, the minimum <NUM> is offset from the sign change <NUM>. Generally, the period <NUM> separating the positive-to-negative sign change and the minimum pressure measurement can be a multiple of the segment width (b*SW). In that regard, the multiple can be greater than, equal to, or less than one (b > <NUM>, b = <NUM>, or b < <NUM>) in different embodiments. For example, the multiple (c) can be between about <NUM> and about <NUM>, about <NUM> and about <NUM>, about <NUM> and about <NUM>, including values such as <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and/or other suitable values both larger and smaller. Similarly, the minimum <NUM> can occur at a time <NUM>, prior to the time <NUM> associated with the sign change <NUM>. Thus, the minimum <NUM> is offset from the sign change <NUM>. The period <NUM> separating the times <NUM>, <NUM> can be a multiple of the segment width. In that regard, because the minima <NUM>, <NUM> are associated with different heart beat cycles, the periods <NUM>, <NUM> can be different in some instances.

The value of the segment slope waveform <NUM> changes from negative to positive at times <NUM> and <NUM>. The locations <NUM>, <NUM> in segment slope waveform <NUM> correspond to these negative-to-positive sign changes. The maxima <NUM>, <NUM> of the pressure waveform <NUM> can be identified based on the location the sign of the segment slope waveform <NUM> changes from negative to positive. For example, the maximum <NUM> can occur at a time <NUM>, prior to the time <NUM> associated with the sign change <NUM>. In an embodiment, the time <NUM> occurs at <NUM>% of the segment width before the time <NUM>. Thus, the maximum <NUM> can be offset from the sign change <NUM>. Generally, the period <NUM> separating the negative-to-positive sign change and the peak pressure measurement can be a multiple of the segment width (c*SW). In that regard, the multiple can be greater than, equal to, or less than one (c > <NUM>, c = <NUM>, or c < <NUM>) in different embodiments. For example, the multiple (c) can be between about <NUM> and about <NUM>, about <NUM> and about <NUM>, about <NUM> and about <NUM>, including values such as <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and/or other suitable values both larger and smaller. Similarly, the maximum <NUM> can occur at a time <NUM>, prior to the time <NUM> associated with the sign change <NUM>. Thus, the maximum <NUM> can be offset from the sign change <NUM>. The period <NUM> separating the times <NUM>, <NUM> is a multiple of the segment width. In the regard, because the maxima <NUM>, <NUM> are associated with different heart beat cycles, the periods <NUM>, <NUM> can be different in some instances.

The feature plot <NUM> illustrates the location of the minima (valley) and maxima (peak) of the pressure waveform <NUM>. In that regard, the valley (n-<NUM>) <NUM>, associated with a cardiac cycle (n-<NUM>), is aligned with the time <NUM> that occurs a period <NUM> before the positive-to-negative sign change <NUM>. The valley (n) <NUM>, associated with the next cardiac cycle (n), is aligned with the time <NUM> that occurs a period <NUM> before the positive-to-negative sign change <NUM>. The peak (n-<NUM>) <NUM>, associated with a cardiac cycle (n-<NUM>), is aligned with the time <NUM> that occurs a period <NUM> before the negative-to-positive sign change <NUM>. The peak (n) <NUM>, associated with the next cardiac cycle (n), is aligned with the time <NUM> that occurs a period <NUM> before the negative-to- positive sign change <NUM>.

Referring now to <FIG>, shown therein is a graphical representation <NUM> of selecting the diagnostic window <NUM>. The starting point <NUM> and/or the ending point <NUM> of the diagnostic window <NUM> can be selected based on the sign change(s) of the slope. For example, the diagnostic window can be selected using the identified minima <NUM>, <NUM> and maxima <NUM>, <NUM> based on the sign change(s) in the slope of the pressure waveform. In some embodiments, the starting point <NUM> of the diagnostic window <NUM> can be offset from the peak pressure measurement, and the ending point <NUM> can be offset from the minimum pressure measurements. In some embodiments, the starting point <NUM> and/or the ending point <NUM> can selected based on different slope sign changes. For example, the starting point <NUM> can be selected based on a negative-to-positive slope sign change, and the ending point <NUM> can be selected based on a positive-to-negative slope sign change. In some embodiments, the starting point <NUM> can be offset from the negative-to-positive sign change, and the ending point <NUM> can be offset from the positive-to-negative sign change.

In some embodiments, a computing device can identify the maximum negative/down slope <NUM> that occurs after the maximum or peak pressure value <NUM>. The diagnostic window <NUM> can be selected within the period <NUM> between the maximum negative/down slope value <NUM> and the next minimum pressure value <NUM>. In that regard, the computing device can select a beginning point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the period <NUM> from the time <NUM>. That is, the beginning point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the maximum negative/down slope value <NUM>. A computing device can select an ending point <NUM> of the diagnostic window <NUM> to be positioned a fixed percentage of the period <NUM> from the time <NUM>. That is, the ending point <NUM> of the diagnostic window can be offset by a period <NUM> from the time <NUM> of the next minimum pressure value <NUM>. One, the other, or both of the periods <NUM>, <NUM> can be described as a percentage of the period <NUM>, including values between about <NUM>% and about <NUM>%, between about <NUM>% and about <NUM>%, between about <NUM>% and <NUM>%, as <NUM>%, <NUM>%, <NUM>%, and/or other suitable values both larger and smaller. For example, the period <NUM> can be <NUM>% of the period <NUM>, and the period <NUM> can be <NUM>% of the period <NUM>.

Referring now to <FIG>, shown therein is flow diagram of a method <NUM> of evaluating a vessel of a patient. As illustrated, the method <NUM> includes a number of enumerated steps, but implementations of the method <NUM> may include additional steps before, after, and in between the enumerated steps. In some implementations, one or more of the enumerated steps may be omitted or performed in a different order. One or more of the steps of the method <NUM> may be performed by processing unit or processor, such as the computing device <NUM> (<FIG>). One or more of the steps of the method <NUM> can be carried out by a user, such as a cardiologist or other medical professional.

At step <NUM>, the method <NUM> includes introducing a first intravascular pressure-sensing instrument into a vessel of a patient proximal of a stenosis of vessel. In some examples, a catheter, guide wire, or a guide catheter with a pressure sensor can be inserted into, e.g., a coronary artery such that at least a portion of the instrument (e.g., the portion including the pressure sensor) is positioned proximal of a stenosis of the vessel. At step <NUM>, the method <NUM> includes introducing a second intravascular pressure-sensing instrument into the vessel distal of the stenosis of the vessel. In some examples, a catheter, guide wire, or a guide catheter with a pressure sensor can be inserted into, e.g., a coronary artery such that at least a portion of the instrument (e.g., the portion including the pressure sensor) is positioned distal of the stenosis of the vessel. In some examples, the intravascular pressure-sensing instrument positioned proximally of the stenosis is a catheter or guide catheter, and the intravascular pressure-sensing instrument positioned distally of the stenosis is a guide wire.

At step <NUM>, the method <NUM> includes receiving, at a computing device of an intravascular processing system, proximal and distal pressure measurements respectively obtained by first and second intravascular pressure-sensing instruments. The computing device is in communication with first and second intravascular pressure-sensing instruments. The proximal and distal pressure measurements can be obtained during one or more cardiac cycles of the patient. The proximal and distal pressure measurements can be obtained without administration of a hyperemic agent to the patient.

At step <NUM>, the method <NUM> includes selecting, by the computing device of the intravascular processing system, a diagnostic window within the cardiac cycle of the patient. The diagnostic window encompasses only a portion of the cardiac cycle of the patient. In some examples, the selecting a diagnostic window does not include using electrocardiogram (ECG) data to, e.g., identify a beginning of a cardiac cycle. The diagnostic window can be selected by identifying a change in sign of a slope associated with at least one of the proximal pressure measurements or the distal pressure measurements. In that regard, the method <NUM> can calculating the slope over multiple time periods. In some examples, a single time period encompasses only a portion of the cardiac cycle. In some examples, time periods associated with a single cardiac cycle have the same duration. In some examples, a computing device or processing unit calculates the slope over time periods of multiple cardiac cycles. The time periods associated with a first cardiac cycles can have different duration than the time periods associated with the second cardiac cycle. In some examples, a duration of the time periods is based on a duration of time periods in one or more previous cardiac cycles. In some examples, a duration of a time period is based on an average of earlier time period durations. In some examples, consecutive time periods at least partially overlap in time. In some examples, a starting point of consecutive time periods are offset based on an acquisition rate of the at least one pressure-sensing instrument.

The method <NUM> can include identifying a sign change of the slope based on the slope calculated over the plurality of time periods. That is, slopes respectively associated with the plurality of segments can change polarity or sign from positive to negative or from negative to positive. The method <NUM> can include determining, based on the sign change of the slope, a minimum pressure measurement, a peak pressure measurement, a beginning of the cardiac cycle, an ending of the cardiac cycle, a beginning of systole, an ending of diastole, a starting point of the diagnostic window, and/or an ending point of the diagnostic window.

In some examples, the diagnostic window can be selected based on the time during the cardiac cycle at which the sign of the slopes changes. A computing device or processing unit can determine a starting point of the diagnostic window based on the sign change of the slope. The starting point of the diagnostic window can be offset from the sign change of the slope. In some embodiments, a peak pressure measurement can be determined based on the sign change of the slope. The peak pressure measurement can be offset from the sign change of the slope. A computing device or processing unit can determine a starting point of the diagnostic window based on the peak pressure measurement. The starting point of the diagnostic window can be offset from the peak pressure measurement. In some examples, the method <NUM> further determining a maximum negative slope occurring after the peak pressure measurement. For example, the maximum negative slope point can occur between an identified peak pressure measurement (cardiac cycle n-<NUM>) and a next identified minimum pressure measurement (cardiac cycle n). A computing device or processing unit can determine a starting point of the diagnostic window based on the maximum negative slope. The starting point of the diagnostic window can be offset from the maximum negative slope.

In some examples, the method <NUM> further includes determining a second or further sign change of the slope. A computing device or processing unit can determine a minimum pressure measurement based on the further sign change of the slope. The minimum pressure measurement can be offset from the further sign change of the slope. A computing device or processing unit can determine an ending point of the diagnostic window based on the minimum pressure measurement. The ending point of the diagnostic window can be offset from the minimum pressure measurement.

At step <NUM>, the method <NUM> includes identifying, by the computing device of the intravascular processing system, a plurality of the distal pressure measurements obtained during the diagnostic window from the received distal pressure measurements. The plurality of distal pressure measurements are selected based on the selected diagnostic window and are a subset of the received distal pressure measurements. Step <NUM> similarly includes identifying, by the computing device of the intravascular processing system, a plurality of the proximal pressure measurements obtained during the diagnostic window from the received proximal pressure measurements. The plurality of proximal pressure measurements are selected based on the selected diagnostic window and are a subset of the received proximal pressure measurements. An example of identifying a plurality of the pressure measurements obtained during the diagnostic window is described in <CIT> (published as <CIT>).

At step <NUM>, the method <NUM> includes calculating, by computing device, a pressure ratio between an average of the plurality of distal pressure measurements obtained during the diagnostic window and an average of the plurality of proximal pressure measurements obtained during the diagnostic window. An example of calculating the pressure ratio is described in <CIT> (published as <CIT>).

At step <NUM>, the method <NUM> includes outputting the calculated pressure ratio to display device in communication with computing device. In some examples, the proximal and distal pressure measurements are aligned (with respect to time) before the pressure ratio is calculated, as described, for example, in <CIT> (published as <CIT>); and/or <CIT> (published as <CIT>). For example, alignment can be performed when the user selects a normalization option provided by the intravascular system. Once the normalization is ordered, the amount of misalignment is calculated by cross-correlating the proximal and distal pressure measurements pressure for every heart cycle until the fifth cycle. To complete the normalization, the pressure measurements, for each heart cycle, can be shifted by an average of the five cycles.

At step <NUM>, the method <NUM> includes identifying a treatment option based on the calculated pressure ratio. For example, the treatment option can be no treatment, drug therapy, a percutaneous coronary intervention (PCI), such as angioplasty and/or stenting, a coronary artery bypass grafting (CABG) procedure, and/or other suitable clinical interventions including combinations of the foregoing options. At step <NUM>, the method <NUM> includes performing the identified treatment option.

Claim 1:
An intravascular system comprising:
at least one pressure-sensing instrument sized and shaped for introduction into a vessel of a patient;
a processing unit in communication with the at least one pressure-sensing instrument, the processing unit configured to:
obtain proximal pressure measurements for at least one cardiac cycle of the patient from the at least one pressure-sensing instrument while the at least one pressure-sensing instrument is positioned within the vessel at a position proximal of a stenosis of the vessel;
obtain distal pressure measurements for the at least one cardiac cycle of the patient from the at least one pressure-sensing instrument while the at least one pressure-sensing instrument is positioned within the vessel at a position distal of the stenosis of the vessel;
select a diagnostic window within a cardiac cycle based on at least one feature of the cardiac cycle of the patient by identifying a change in sign of a segment slope waveform associated with the at least one feature of the cardiac cycle through a period-by-period or segment-by-segment analysis of slopes of segments of a pressure waveform of the proximal pressure measurements or the distal pressure measurements, wherein the diagnostic window encompasses only a portion of the cardiac cycle of the patient;
calculate a pressure ratio between the distal pressure measurements obtained during the diagnostic window and the proximal pressure measurements obtained during the diagnostic window; and
output the calculated pressure ratio to a display device in communication with the processing unit.