Catheter for intravenous physiological assessment

Abstract

A catheter for intravenous physiological and structural assessment includes a tube defining a guide wire lumen. A sensor assembly is mounted on the tube. The sensor assembly includes an ultrasound transducer array and a pressure sensor. Electrical conductors are positioned around the tube for communicating electrical signals to and from the sensor assembly. An outer layer surrounds the electrical conductors. A cross-section of the catheter including the tube, the electrical conductors, and the outer layer has a diameter of 0.023 inches or less.

Description

CATHETER FOR INTRAVENOUS PHYSIOLOGICAL ASSESSMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is being filed as a PCT international application and claims the benefit of and priority7to U.S. Provisional Patent Application No. 63 / 661,959, filed June 20, 2024, and U.S. Provisional Patent Application No. 63 / 639,022, filed April 26, 2024, the entire disclosures of which are incorporated by reference herein in their entireties.BACKGROUND

[0002] Diagnostic imaging and sensing is typically performed to guide catheterbased interventions inside blood vessels. A common type of diagnostic sensing device is a pressure-sensing wire or micro-catheter. A pressure-sensing wire or micro-catheter is typically used to determine physiological details of a diseased blood vessel, such as whether a lesion is inducing ischemia in a patient. This can be done by measuring blood pressure distal of a coronary7lesion or obstruction, and calculating a ratio of the distal blood pressure divided by an inlet or aortic blood pressure. The ratio can then be compared to a threshold ratio to determine when a lesion is flow limiting and thus ischemia inducing. For example, when the ratio is below a clinically derived threshold, an intervention is typically recommended. Conversely, when the pressure ratio is above the threshold, the intervention can be safely deferred. Accordingly, a pressure-sensing wire or micro-catheter is especially useful in determining when or when not to intervene.

[0003] Clinical evidence has shown that angiographic (i.e. , x-ray imaging with contrast dye injection) narrowing in the intermediate range (typically 50-70% stenosis) is frequently not flow limiting and an intervention (e.g., balloon angioplasty or stent implantation) would result in harm to the patient. In diffuse disease states (e.g., when there is a presence of multiple lesions or obstructions), a pressure-sensing wire or micro-catheter is useful to identify which lesion, among many, is primarily responsible for limiting the blood flow Accordingly, a pressure wire or micro-catheter, is used to determine when to intervene and when to defer intervention. Further, once an intervention is determined to be warranted, the pressure-sensing wire or micro-catheter is useful in determining which lesion or lesions, among many, is flow limiting and would benefit the most from an intervention such as implanting a stent into the blood vessel.

[0004] Early clinical evidence suggests that a post-intervention pressure ratio may be useful to assess the restoration of normal blood flow. The post-intervention pressure ratio typically has a higher clinically derived threshold. This higher threshold may be beneficial for long term prognosis (i.e., associated with reduced major adverse cardiac events over time.) When a post intervention pressure ratio is below the higher threshold, the interventionalist may elect to further intervene, typically with an additional larger high pressure balloon to further expand the stent.

[0005] Another common type of diagnostic imaging device is an intravascular ultrasound (IVUS) imaging catheter. An IVUS imaging catheter is often delivered to a region of interest within a blood vessel to visualize structural details of the blood vessel. An IVUS imaging catheter provides increased detail and accuracy of structural detail over angiography. The structural detail of the coronary vasculature is especially important during an intervention.

[0006] For example, measurements derived from IVUS imaging can be used to determine an average coronary’ diameter both proximally and distally of a lesion or obstruction, which can be used to determine an ideal diameter of a coronary stent. Further, IVUS imaging can be used to determine both distal and proximal stent landing zones, ty pically regions with less than 50% stenosis, and can be used to determine an optimal length for the stent.

[0007] IVUS imaging is further useful in determining the composition of cardiovascular disease. For example, IVUS imaging can be used to determine whether calcium deposits are likely to inhibit proper expansion of a coronary’ stent. Thus, IVUS imaging can be used to determine whether to pre-treat calcium deposits to insure proper stent expansion.

[0008] After the placement of a coronary stent, IVUS imaging is useful in assessing whether the stent is fully expanded and properly positioned against the arterial wall. During post stent imaging, the operator will also use IVUS imaging to confirm that the placement of the stent did not result in any dissections, tears, or flaps at the edges of the stent.

[0009] Finally, IVUS imaging can be used to determine whether a minimum diameter or a minimum luminal area within the stent has been reached.Interventional! sts can use different methods and criteria to determine optimal stent expansion. For example, when determining a minimal in stent diameter, the distal "‘near normal” average diameter may be used. Alternatively, a slightly more aggressivetechnique would be to use the distal external elastic membrane (i.e., normal vessel wall without disease) as the target minimum in stent diameter.

[0010] When assessing the minimal stented luminal area, a minimum 5 mm2is commonly used. For smaller vessels, where 5 mm2is not achievable (i.e., when the distal “near normal” luminal area is 5 mm2or less) the measured distal luminal area minus 0.5 mm2may be used to determine the target minimum stent area.

[0011] Furthermore, when stents are very long, such that the distal segment is significantly smaller than the proximal segment, a two-balloon technique with one larger balloon and one smaller balloon may be employed where the distal diameter or luminal area is achieved for the distal segment of the stent and the proximal diameter or luminal area is utilized for the proximal segment of the stent. When such criteria are achieved, one year outcome data indicates clinically significant reductions in major adverse cardiovascular events (MACE).

[0012] Given the foregoing, pressure ratios are used to determine when and where to intervene or when to defer an intervention, whereas IVUS measurements and imaging is used to select the stent diameter and length, to correctly position the stent, to confirm optimal stent expansion, and to identify and evaluate any stent edge issues. Thus, a pressure-sensing wire or micro-catheter and an IVUS imaging catheter are complimentary tools that when used together can improve patient outcomes.

[0013] Combining both IVUS imaging and pressure sensing on an intravenous catheter eliminates the need for separate devices and streamlines clinical workflows, thereby reducing time and costs associated with diagnostic imaging and sensing. However, the size of an IVUS imaging catheter can influence blood flow in the blood vessel, which can cause inaccurate blood pressure measurements by the pressuresensing wire or micro-catheter.SUMMARY

[0014] In general terms, the present disclosure relates to a catheter for intravenous physiological assessment. In one possible configuration, the catheter has a reduced cross-section that mitigates influence on blood flow inside a blood vessel. Various aspects are described in this disclosure, which include, but are not limited to, the following aspects.

[0015] One aspect relates to a catheter for intravenous physiological and structural assessment, the catheter comprising: a tube defining a guide wire lumen; a sensor assembly mounted on the tube, the sensor assembly including: an ultrasound transducerarray; and a pressure sensor; electrical conductors positioned around the tube for communicating electrical signals to and from the sensor assembly; and an outer layer surrounding the electrical conductors, wherein a cross-section of the catheter including the tube, the electrical conductors, and the outer layer has a diameter of 0.023 inches or less.

[0016] Another aspect relates to a method of manufacturing a catheter for insertion into a blood vessel, the method comprising: obtaining a tube having a lumen for a guide wire; mounting a sensor assembly on the tube, the sensor assembly including an ultrasound transducer array and a pressure sensor; mounting electrical conductors around the tube for communicating electrical signals to and from the sensor assembly; and applying an outer layer around the electrical conductors, wherein a cross-section of the catheter including the tube, the electrical conductors, and the outer layer is 0.023 inches or less.

[0017] Another aspect relates to a catheter for intravenous physiological and structural assessment, the catheter comprising: a tube defining a guide wire lumen, the tube made of a polymer material having embedded therein wires that surround the guide wire lumen, the tube having a wall thickness of 0.003 inches, and the wires each having a diameter less than 0.0025 inches; and a sensor assembly mounted on the tube, the sensor assembly coupled to the wires embedded in the tube for communicating electrical signals to and from the sensor assembly, and the sensor assembly including: an ultrasound transducer array; and a pressure sensor.

[0018] Another aspect relates to a method of determining when to perform an intervention inside a blood vessel, the method comprising: capturing a first pressure reading using a distal pressure sensor when a sensor assembly is positioned across a region of interest; capturing a second pressure reading using a proximal pressure sensor when the sensor assembly remains positioned across the region of interest; calculating a pressure ratio between the first pressure reading and the second pressure reading; comparing the pressure ratio to a threshold; and recommending the intervention when the pressure ratio is less than the threshold.

[0019] A variety of additional aspects will be set forth in the description that follows. The aspects can relate to individual features and to combination of features. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the broad inventive concepts upon which the examples disclosed herein are based.DESCRIPTION OF THE FIGURES

[0020] The following drawing figures, which form a part of this application, are illustrative of the described technology and are not meant to limit the scope of the disclosure in any manner.

[0021] FIG. 1 is an isometric view of an example of a catheter for intravenous physiological and structural assessment.

[0022] FIG. 2 is an isometric view of a distal end of the catheter of FIG. 1.

[0023] FIG. 3 is a front view of the distal end of the catheter of FIG. 1.

[0024] FIG. 4 is a detailed isometric view of the distal end of the catheter of FIG. 1.

[0025] FIG. 5 is another isometric view of the distal end of the catheter of FIG. 1.

[0026] FIG. 6 is a cross-sectional view of the distal end of the catheter of FIG. 1 taken across the broken line FIG. 6 - FIG. 6 shown in FIG. 3.

[0027] FIG. 7 is an isometric view of a proximal end of the catheter of FIG. 1.

[0028] FIG. 8 is a side cross-sectional view of a reduced cross-section portion and a transition portion of the catheter taken across the broken line FIG. 8 - FIG. 8 shown in FIG. 3.

[0029] FIG. 9 is another side cross-sectional view- of the reduced cross-section portion and the transition portion of the catheter taken across the broken line FIG. 9 - FIG. 9 in FIG. 3.

[0030] FIG. 10 is a top cross-sectional view of the reduced cross-section portion and the transition portion of the catheter taken across the broken line FIG. 10 - FIG. 10 shown in FIG. 3.

[0031] FIG. 11 is a top view of the catheter of FIG. 1.

[0032] FIG. 12 is a cross-sectional view of the catheter of FIG. 1 taken along the broken line FIG. 12 - FIG. 12 shown in FIG. 11.

[0033] FIG. 13 is a cross-sectional view- of a sensor assembly of the catheter of FIG. 1 taken along the broken line FIG. 13 - FIG. 13 shown in FIG. 11.

[0034] FIG. 14 is a cross-sectional view of a mandrel housing of the catheter of FIG. 1 taken along the broken line FIG. 14 - FIG. 14 shown in FIG. 11.

[0035] FIG. 15 is a cross-sectional view- of a distal tip proximal of the sensor assembly of the catheter of FIG. 1 taken along the broken line FIG. 15 - FIG. 15 shown in FIG. 11.

[0036] FIG. 16 is a cross-sectional view of a reduced cross-section portion of the catheter of FIG. 1 taken along the broken line FIG. 16 - FIG. 16 shown in FIG. 11 .

[0037] FIG. 17 is a cross-sectional view of a transition portion of the catheter of FIG. 1 taken along the broken line FIG. 17 - FIG. 17 shown in FIG. 11.

[0038] FIG. 18 is a cross-sectional view of the catheter of FIG. 1 taken along the broken line FIG. 18 - FIG. 18 shown in FIG. 11.

[0039] FIG. 19 is a cross-sectional view of the catheter of FIG. 1 taken along the broken line FIG. 19 - FIG. 19 shown in FIG. 11.

[0040] FIG. 20 schematically illustrates an example of a method of manufacturing the catheter of FIG. 1.

[0041] FIG. 21 is a cross-sectional view of another example of the reduced crosssection portion of the catheter of FIG. 1.

[0042] FIG. 22 is a cross-sectional view of another example of the reduced crosssection portion of the catheter of FIG. 1.

[0043] FIG. 23 schematically illustrates an example of a method of determining when to perform an intervention using the catheter of FIG. 1.

[0044] FIG. 24 is an isometric view of the distal end of another example embodiment of the catheter for intravenous physiological and structural assessment.

[0045] FIG. 25 is an isometric view of the distal end of the example embodiment of the catheter of FIG. 24 w ith the distal tip shown in phantom.

[0046] FIG. 26 is a cross-sectional isometric view of the distal end of the example embodiment of the catheter of FIG. 24.DETAILED DESCRIPTION

[0047] FIG. 1 is an isometric view' of an example of a catheter 100 for intravenous physiological and structural assessment. The catheter 100 is structured for imaging a blood vessel and measuring blood pressure inside the blood vessel. The catheter 100 has a reduced cross-section to mitigate influence on blood flow w hen the catheter 100 is positioned inside the blood vessel. By mitigating the influence on blood flow, the reduced cross-section of the catheter 100 improves the accuracy of the blood pressure measurements captured by the catheter 100.

[0048] As shown in FIG. 1, the catheter 100 extends between a distal end 102 and a proximal end 104. The catheter 100 includes a sensor assembly 106 positioned tow ard the distal end 102, and ajunction box 108 positioned toward the proximal end 104. The junction box 108 provides a region for housing excess electrical transmission line for device assembly. The catheter 100 can further include a strain relief member 152 to mitigate strain.

[0049] Proximal of the junction box 108, the transmission line is encapsulated into an outer jacket and forms a cable assembly 109. The cable assembly 109 extends from the proximal end 104 of the catheter 100 to a multi -pin connector for interfacing to an imaging and sensing console. In some examples, the multi-pin connector is detachable and disposable. The length of the cable assembly 109 is sufficiently long to extend from an end of a guide catheter within the sterile field to a non-sterile bedside connector that is part of the imaging and sensing console. The length of the cable assembly 109 is approximately 30 inches or longer.

[0050] FIG. 2 is an isometric view of the distal end 102 of the catheter 100. FIG. 3 is a front view of the distal end 102 of the catheter 100. FIG. 4 is a detailed isometric view of the distal end 102 of the catheter 100. FIG. 5 is another isometric view of the distal end 102 of the catheter 100. FIG. 6 is a cross-sectional view of the distal end 102 of the catheter 100 taken across the broken line show n in FIG. 3. As shown in FIGS. 1- 6, the catheter 100 includes a tube 110 defining a guide wire lumen 112. The guide wire lumen 112 includes a guide wire entry port 114 and a guide wire exit port 116 (see FIGS. 1. 6. and 7). and a length L of the tube 110 (see FIG. 1) extends between the guide wire entry port 114 and the guide wire exit port 1 16.

[0051] The catheter 100 has a long rail catheter design that can be safer than a short rail catheter design due to guide wire entanglement, which can occur with short rail catheter designs. Guide wire entanglement most commonly occurs during catheter extraction when the catheter catches on the guide wire and the operator continues to pull on the catheter such that the guide ware prolapses and becomes entangled on the catheter. When guide wire entanglement occurs, the operator typically has to remove both the guide wire and the catheter, which can result in loss of distal guide wire position, thus requiring re-insertion of a new guide wire.

[0052] The guide wire lumen 112 is extended through the catheter 100 such that the guide wire lumen 112 covers the guide wire outside the guide catheter thereby mitigating the potential for guide wire entanglement. In some examples, the length L of the tube 110 and / or the guide wire lumen 112 is about seven inches or more.

[0053] As shown in FIG. 3, the tube 110 has an inner diameter (ID) for the guide wire lumen 112 to accommodate a guide wire. The inner diameter (ID) allows the guide wire lumen 112 to accommodate a 0.014 inch guide wire. In some examples, the inner diameter (ID) is about 0.016 inches to provide a clearance of about 0.002 inches for smoothly passing the guide wire through the guide wire lumen 112 of the tube 110. Theguide wire lumen 112 can be lined or coated with a non-stick material such as polytetrafluoroethylene (PTFE) to reduce friction between the guide wire and the guide wire lumen 112, thus ensuring that the guide wire smoothly passes through the guide wire lumen 112. In some examples, the tube 110 has a wall thickness of 0.001 inches. In such examples, the tube 110 has an outside diameter of 0.018 inches. It is contemplated that the wall thickness of the tube 110 may be adjusted to add tensile strength to the tube 110. or to reduce the outer diameter and profile of the tube 110 as desired.

[0054] In some examples, the tube 110 is made of polyimide material. In some examples, the tube 110 exhibits a tensile strength at break greater than 3N.

[0055] The tube 110 has a beveled edge 118 at the guide wire entry port 114. The beveled edge 1 18 allows the catheter 100 to traverse obstructions inside a blood vessel when being advanced through the blood vessel for intravenous structural and physiological assessment.

[0056] The catheter 100 includes a distal tip 120 mounted on the tube 110 at the distal end 102 of the catheter 100. The distal tip 120 is made of flexible polymer material. The distal tip 120 includes a beveled edge 122 that can align with the beveled edge 118 of the tube 110. The polymer material and beveled edge 122 of the distal tip 120 allows the catheter 100 to traverse obstructions inside the blood vessel when being advanced through the blood vessel.

[0057] As shown in FIGS. 5 and 6, the sensor assembly 106 is mounted on the tube 110 such that the sensor assembly 106 surrounds the guide wire lumen 112. The sensor assembly 106 includes an ultrasound transducer array 124 that surrounds the guide wire lumen 112, and a distal pressure sensor 126. Aspects of the sensor assembly 106 are described in U.S. Patent Application No. 16 / 991,745, filed on August 12, 2020, entitled MULTIPLE SENSOR CATHETER ASSEMBLY, the disclosure of which is hereby incorporated by reference in its entirety.

[0058] In some examples, the distal pressure sensor 126 is a half bridge pressure sensor. The sensor assembly 106 can include several various sized and voltage rated capacitors, a plurality of application-specific integrated circuits (ASIC) 128 each having a multiplexer (MUX) for transmitting ultrasound signals on one or more elements of the ultrasound transducer array 124, and for receiving ultrasound signals on one or more elements of the ultrasound transducer array 124, and a matched pair of resistors for completing a Wheatstone bridge pressure sensing circuit. In someexamples, the sensor assembly 106 includes a pair of half bridge resistors within the ASICs 128 that can eliminate pressure drift from resistance changes inherent in long, small gage wires or traces. In some examples, the pair of half bridge resistors are positioned at a bottom of the sensor assembly 106. The distal pressure sensor 126 and the plurality7of ASICs 128 are mounted to a mandrel housing 146 that surrounds the tube 110, as shown in FIG. 14.

[0059] The low frequency pressure signals from the distal pressure sensor 126 are amplified within the ASIC 128 and coupled onto a receiver output of the ASIC. In some examples, the plurality7of ASICs 128 further include a low noise amplifier that amplifies the ultrasound signals from the ultrasound transducer array 124 before transmission to the imaging and sensing console. Amplifying the ultrasound signals within the ASICs 128 improves the signal to noise ratio and noise immunity from external interfering signals of the sensor assembly 106. Further, the ASICs 128 can combine the low frequency pressure signals and the high frequency ultrasound signals onto the same receiver output for transmission to the imaging and sensing console.

[0060] The sensor assembly 106 enables the imaging acquired from the ultrasound transducer array 124 to be utilized for positioning the sensor assembly 106 in a region within an artery7that has minimal obstructive cardiovascular disease (e.g., <50% stenosis or “near normal”). This ensures that the larger cross-sectional area of the sensor assembly 106 (compared to a reduced cross-section portion 136 described further below) does not impede blood flow and adversely influence the pressure readings from the distal pressure sensor 126.

[0061] As further shown in FIG. 6, electrical conductors 130 are coupled to the sensor assembly 106 by soldering, welding, anisotropic conductive film adhesive (e.g., tape), or other means for communicating electrical signals to and from the sensor assembly 106. The electrical conductors 130 can be positioned around the tube 110. In one example, the electrical conductors 130 include a substrate 132 having a plating of one or more layers of conductive material with portions of the plating of the one or more layers of conductive material removed by etching, ablation, or other technique to form electrical traces 133 on the substrate 132. The substrate 132 is shaped to surround the tube 110. The substrate 132 and the electrical traces 133 run along a length of the reduced cross-section portion 136 of the catheter 100.

[0062] In another example, the electrical conductors 130 include a plating of one or more layers of conductive material applied on an outside surface of the tube 110. In thisexample, portions of the plating of the one or more layers of conductive material can be removed from the outside surface of the tube 110 by etching, ablation, or other technique to form the electrical traces 133 directly on the outside surface of the tube 110. The electrical traces 133 are coupled to the sensor assembly 106 for communicating the electrical signals to and from the sensor assembly 106 along the length of the reduced cross-section portion 136 of the catheter.

[0063] In another example, the electrical conductors 130 include one or more layers of conductive material printed on the outside surface of the tube 110 to form the electrical traces 133 on the outside surface of the tube 110. In this example, the electrical traces 133 are coupled to the sensor assembly 106 for communicating electrical signals to and from the sensor assembly 106 along the length of the reduced cross-section portion 136 of the catheter 100.

[0064] The layers of conductive material that form the electrical traces 133 can include a 0.25oz-in2flexible circuit metallurgy that can include, for example, one or more layers of copper (Cu), nickel (Ni), and gold (Au). The electrical traces 133 can include eight traces, with three of the eight traces for power transmission to the sensor assembly 106 and five of the eight traces for communications transmission to and from the sensor assembly 106.

[0065] The electrical traces 133 can be about 0.005 inches thick. The electrical traces 133 can be about 0.003 inches wide (85 microns) and that are about 0.003 inches (75 microns) spaced apart. The width of the traces and the spacing of the traces can be varied, depending on the characteristics of the signals they carry. For example, power traces may be wider than non-power traces to lower resistance and increase current carrying capacity’. In another example, electrical traces 133 that are adjacent can be designed to have a specific width and spacing to control the impedance along the length of the reduced cross-section portion 136 of catheter 100. For example, an impedance between 80 to 115 ohms may be advantageous in certain instances.

[0066] As shown in FIG. 6, the catheter 100 includes an outer layer 134 surrounding the electrical conductors 130. The outer layer 134 seals the electrical traces 133 from exposure to bodily fluids such as blood when the catheter 100 is inside a blood vessel. In some examples, the outer layer 134 is a heat shrink tubing made of a thermoplastic polymer such as polyethylene terephthalate (PET). Alternatively, the outer layer 134 can include an insulative coating.

[0067] As shown in FIGS. 5, an aperture 127 is cut into the sensor assembly 106 such that the distal pressure sensor 126 is exposed to fluids such as blood allowing the distal pressure sensor 126 to directly measure a distal blood pressure. The aperture 127 is shaped to prevent air bubbles from forming. For example, the aperture 127 has a square, rectangular, or ellipse shape.

[0068] Further, the imaging acquired from the ultrasound transducer array 124 can be utilized to image in a direction that the aperture 127 faces to ensure that the aperture 127 is not against a wall of the blood vessel or artery, which may impede the pressure readings captured by the distal pressure sensor 126. When imaging detects that the aperture 127 is against a wall of the blood vessel or artery , the proximal end 104 of the catheter 100 that is outside of the patient can be rotated such that the aperture 127 is rotated away from the wall of the blood vessel or artery.

[0069] Another aspect of the sensor assembly 106 is the continuous operation of both the distal pressure sensor 126 and the ultrasound transducer array 124. Since the ultrasound transducer array 124 is continuously imaging, the images can be utilized to produce continuous automated segmentation of the lumen and vessel walls. This information is useful for guiding treatment (e.g., stent selection and placement).Automatic segmentation may employ gray scale and / or motion detection techniques, and / or artificial intelligence and machine learning methods.

[0070] Luminal areas can be determined from the IVUS imaging of the ultrasound transducer array 124 to provide oversight of the pressure readings captured by the distal pressure sensor 126. For example, when the sensor assembly 106 is positioned in a region of arterial narrowing, the larger cross-sectional area of sensor assembly 106 mayimpact the pressure readings. In such instances, the luminal area determined from the IVUS imaging can be used to disable the pressure readings from the distal pressure sensor 126, to present a warning to the operator, or to compensate (i.e., correct) for the narrowing and adjust the pressure readings to present corrected pressure reading values using algorithms including artificial intelligence and machine learning.

[0071] The oversight of the pressure readings captured by the distal pressure sensor 126, as provided by the IVUS imaging of the ultrasound transducer array 124, can be useful during a manual pullback of the catheter 100. Manual pullbacks are common and enable the physician to acquire an overall view of the entire vessel from the most distal position of the catheter 100 within the vessel all the way back to the guide catheter. During a manual pullback, the sensor assembly 106 can traverse regions of vesselnarrowing, and pressure readings may change when this occurs. The above-described IVUS imaging oversight techniques can aid in monitoring structural changes affecting pressure readings during manual pullback of the catheter 100.

[0072] FIG. 7 is an isometric view of the proximal end 104 of the catheter 100. As shown in FIG. 7, the guide wire exit port 116 of the tube 110 is located toward the proximal end 104.

[0073] As shown in FIGS. 1, 2, 5. 6, and 7, the reduced cross-section portion 136 is positioned between the sensor assembly 106 and a transition portion 138 of the catheter 100, which is described in more detail below. In some examples, the reduced crosssection portion 136 has a length of about 4 inches or more. In some examples, the reduced cross-section portion 136 has a length between about 6 inches and 7 inches. The length of the reduced cross-section portion 136 is such that the impact on the flow of blood through the diseased portion of the artery under investigation is minimized and the transition portion 138 remains inside the guide catheter.

[0074] As shown in FIG. 6, the reduced cross-section portion 136 includes the tube 110, the electrical conductors 130. and the outer layer 134. The reduced cross-section portion 136 has a cross-sectional shape that is substantially circular. The reduced crosssection portion 136 has a size to mitigate influence on blood flow such that the reduced cross-section portion 136 improves the accuracy of the blood pressure measurements captured by the distal pressure sensor 126. The reduced cross-section portion 136 can have a diameter of about 0.023 inches or less, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0004 inches2.

[0075] In some examples, the reduced cross-section portion 136 has a diameter of about 0.020 inches or less. For example, the electrical traces 133 can have a thickness of about 0.0005 inches such that the outside diameter of the tube 110 increases from about 0.018 inches without the electrical traces 133 to about 0.019 inches with the electrical traces. The outer layer 134 can have a wall thickness of about 0.0005 inches such that the total outside diameter of the reduced cross-section portion 136 of the catheter 100 may be as low as about 0.020 inches, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0003 inches2.

[0076] In examples where the electrical traces 133 are plated or printed on the substrate 132 instead of being plated or printed directly on the tube 110, the substrate 132 when combined with the electrical conductors 130 has a thickness of about 0.001 inches (e.g., the substrate 132 has a thickness of about 0.0005 inches and the electricaltraces 133 have a thickness of about 0.0005 inches layered on top of the substrate 132). In such examples, the total outside diameter of the reduced cross-section portion 136 of the catheter 100 is about 0.022 inches or less, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0004 inches2. The reduced crosssection portion 136 extending over the diseased portion of the vessel under examination has an area that is less than 1 / 3 of the cross-sectional area of the sensor assembly 106, having a diameter of about 0.043 inches and an area of about 0.0015 inches2.

[0077] FIG. 8 is a side cross-sectional view of the reduced cross-section portion 136 and the transition portion 138 of the catheter 100. FIG. 9 is another side cross- sectional view of the reduced cross-section portion 136 and the transition portion 138 of the catheter 100. FIG. 10 is a top cross-sectional of the reduced cross-section portion 136 and the transition portion 138 of the catheter 100. Referring now to FIGS. 8-10, the transition portion 138 includes electrical wires 140 that are coupled to the electrical traces 133 on the substrate 132 proximate the guide wire exit port 116. As shown in FIG. 8. the electrical wires 140 are coupled via soldering, welding, or other technique to the electrical traces 133 distal of the guide wire exit port 116. In some examples, the electrical wires 140 are small gage electrical wires that transmit electrical power and communications. In some instances, the small gage electrical wires are 38 gage or smaller.

[0078] The electrical wires 140 can include a plurality of twisted wires mixed with twisted pairs of wires for transmitting electrical power and communications. The twisted pairs of wires can further be designed to have a controlled impedance by varying the thickness of the wires, the spacing of the wires, the thickness of the insulator layer, and the dielectric constant of the insulator. The twisted pairs of wires can have a nominal impedance between about 80 to 116 ohms. In some examples, the twisted pairs of wires have a nominal impedance of about 93 ohms.

[0079] The electrical wires 140 can be twisted together. Three wires can provide power transmission to and from the sensor assembly 106. and five wires can provide communications transmission to and from the sensor assembly 106. Of the five wires used for communication, two sets of independently twisted pairs, each having controlled nominal impedance, can be used for high-speed communication to and from sensor assembly 106. The nominal impedance of the two sets of independently twisted pairs is about 93 + / - 13 ohms. The electrical wires 140 are connected to the electrical traces 133 by soldering, welding, or other termination techniques.

[0080] One impedance controlled twisted pair of wires carries Transmit (Tx) signals to the sensor assembly 106, and the other impedance controlled twisted pair of wires provides Receive (Rx) signals from sensor assembly 106 to the imaging and sensing console. The remaining fifth low-speed communication wire provides a low- speed timing signal that initiates TxRx events. Additionally, the fifth low speed wire and the Tx twisted pair of wires are used to program registers within each of the plurality of ASICs 128, thus controlling which element or elements are transmitting and which element or elements are receiving for all TxRx events.

[0081] The transition portion 138 has an outside diameter (OD) that is larger than the diameter of the reduced cross-section portion 136. In some examples, the transition portion 138 has an egg shape cross-sectional area having a long axis and a short axis. The guide wire exit port 116 is positioned on a narrow side of the long axis of the egg shape cross-sectional area. In some examples, the outside diameter (OD) of the transition portion 138 along the long axis is about 0.048 inches and about 0.040 inches along the short axis. The egg shape (compared to a circular shape) further reduces the cross-sectional area of the transition portion 138, which helps to ensure good fluid flow around the catheter 100 in the guide catheter, such as a 5 French guide catheter which has an inner diameter of about 0.058 inches. The electrical wires 140 attach to the electrical traces 133 about seven inches or more away from the distal end 102 of the tube 110. In some examples the electrical wires 140 attach to the electrical traces 133 at about 10 inches from the distal end 102 of the tube 1 10.

[0082] The catheter 100 further includes a proximal pressure sensor 142 mounted on the substrate 132 and under the outer layer 134. In some examples, the proximal pressure sensor 142 is soldered onto the substrate 132. In other examples, the proximal pressure sensor 142 may be a half bridge pressure sensor. In such examples where the half bridge pressure sensor is used, it is advantageous to solder two matched resistors (not shown) on the substrate 132 adjacent to the half bridge pressure sensor to complete the Wheatstone bridge pressure sensor circuit. Placing two matched bottom bridge resistors near the pressure sensor reduces the likelihood of pressure sensing drift from resistance variations inherent in long, small gage wires or traces.

[0083] In another example, the proximal pressure sensor 142 is connected to the electrical traces 133 on the substrate 132 such that the proximal pressure sensor 142 is utilizing the same reference voltage as the distal pressure sensor 126 in the sensor assembly 106. Advantageously, this eliminates the need to compensate for a differencein pressure sensor reference voltages, which simplifies calculation of a ratio of a distal blood pressure (measured by the distal pressure sensor 126) divided by an inlet or aortic blood pressure (measured by the proximal pressure sensor 142). By simplifying the calculation of the pressure ratio, the accuracy and reliability of the calculated pressure ratio is improved.

[0084] The proximal pressure sensor 142 may be of the same type as the distal pressure sensor 126. such that the distal pressure sensor 126 and the proximal pressure sensor 142 have the same slope of the pressure sensor curve, thereby further simplifying the calculation of the pressure ratio without the need to compensate for differences in pressure sensor type and therefore further improving the accuracy and reliability of the pressure ratio calculation.

[0085] By combining the distal pressure sensor 126 and the proximal pressure sensor 142 on the substrate 132, both pressure sensors can be factory calibrated. By having both the distal pressure sensor 126 and the proximal pressure sensor 142 factory7calibrated, a need for a normalization clinical process is eliminated, where a distal pressure reading system is compensated to track the slope of the pressure curve of a proximal aortic pressure reading system. Eliminating the normalization clinical process reduces the chance for errors and saves time. Furthermore, the factory7calibration of the distal pressure sensor 126 and the proximal pressure sensor 142 can ensure that both an absolute pressure reading and a ratio of the two pressure readings is more reliable and accurate compared to other systems utilizing two different pressure sensors and two different pressure sensor reading systems.

[0086] Further, traditional aortic pressure sensor systems typically measure aortic pressure outside the body at the end of a long fluid line that can be about 10 feet long. Air bubbles in a column of fluid in the fluid line can corrupt the aortic pressure readings and must be cleared. Also, when contrast is in the fluid line, the aortic pressure readings are dampened due to the high density of the contrast medium and must be cleared from the line. By incorporating the proximal pressure sensor 142 together with the distal pressure sensor 126. the catheter 100 avoids such issues due to the proximal pressure sensor 142 having a proximity to the aorta.

[0087] The proximal pressure sensor 142 is mounted distal of the guide wire exit port 116. By being proximally positioned in the guide catheter, the proximal pressure sensor 142 can capture blood pressure measurements where the blood is not obstructed by cardiovascular disease or a lesion to ensure the pressure ratio is an accuraterepresentation of the pressure drop caused by the cardiovascular disease or lesion. The pressure ratio can be used to determine a location where to perform an intervention such as to implant a stent within the patient.

[0088] As shown in FIGS. 7 and 10, an aperture 144 is cut into the outer layer 134 such that the proximal pressure sensor 142 is exposed to fluids such as blood such that the proximal pressure sensor 142 can directly measure the aortic pressure. The aperture 144 is shaped to prevent air bubbles from forming inside the fundus. For example, the aperture 144 can be shaped to have a square, rectangular, or ellipse shape.

[0089] FIG. 11 is a top view of the catheter 100. FIG. 12 is a side cross-sectional view of the catheter 100 taken along the broken line FIG. 12 - FIG. 12 in FIG. 11. FIG. 12 shows the tube 110, the distal tip 120, the sensor assembly 106, the mandrel housing 146, the outer layer 134, the reduced cross-section portion 136, the transition portion 138, the electrical wires 140, and the strain relief member 152 of the catheter 100. The tube 110 has an inner diameter of about 0.016 inches, the sensor assembly 106 includes an outer diameter of about 0.043 inches, and the reduced cross-section portion 136 has an outer diameter of about 0.022 inches.

[0090] FIG. 12 further shows a proximal shaft 148 that is coaxial with the tube 110. The proximal shaft defines a lumen 150 for housing the electrical wires 140 received from the transition portion 138 after the tube 110 terminates at the guide wire exit port 116. The proximal shaft 148 can be made of extruded poly etheretherketone (PEEK) or other similar ty pes of materials. The proximal shaft 148 can have an outside diameter (OD) of up to about 0.039 inches to reduce the impact of the proximal shaft 148 on fluid flow in the guide catheter, thus enabling contrast injections while the catheter 100 is inside the guide catheter.

[0091] FIG. 13 is a cross-sectional view of the sensor assembly 106 of the catheter 100 taken along the broken line FIG. 13 - FIG. 13 in FIG. 11. FIG. 13 shows the ultrasound transducer array 124 surrounding the tube 110, the guide wire lumen 112, and the mandrel housing 146. Protrusions 154 on the mandrel housing 146 allow for injection of backing material behind the ultrasound transducer array 124 during assembly of the catheter 100. The backing material can absorb ultrasound pressure signals that are emitted inward towards the tube 110.

[0092] FIG. 14 is a cross-sectional view of the mandrel housing 146 of the catheter 100 taken along the broken line FIG. 14 - FIG. 14 shown in FIG. 11. FIG. 14 shows that the mandrel housing 146 has five sides resembling a pentagon shape in cross-section. The ASICs 128 are mounted to four sides of the mandrel housing 146, and the distal pressure sensor 126 is mounted to one side of the mandrel housing 146. In the example shown in FIG. 14, the ASICs 128 are mounted to the four sides of the mandrel housing 146 that have equal width, while the distal pressure sensor 126 is mounted to a side of the mandrel housing 146 having a shorter width. As shown in FIG. 14, the sensor assembly 106 that includes the ASICs 128 and the distal pressure sensor 126 surround the tube 110 and the guide wire lumen 1 12.

[0093] Additionally, the mandrel housing 146 is electrically conductive and serves as an electrical path connecting the ultrasound transducer array 124 to the ASICs 128 located proximally of the ultrasound transducer array 124. Utilizing the mandrel housing 146 as the electrical return path provides an electrical path from a distal side of the ultrasound transducer array 124 to a proximal side enabling a continuous array while completing the electrical circuit. The mandrel housing 146 may be manufactured on a screw machine using conductive metal such as stainless-steel. Alternatively, the mandrel housing 146 can be manufactured by metal printing.

[0094] FIG. 15 is a cross-sectional view of the distal tip 120 proximal of the sensor assembly 106 of the catheter 100 taken along the broken line FIG. 15 - FIG. 15 shown in FIG. 11. FIG. 15 show s the substrate 132 having the electrical traces 133 surrounding the tube 110 and the guide wire lumen 112. The electrical traces 133 bring electrical power to the sensor assembly 106 and provide communications to and from the sensor assembly 106.

[0095] FIG. 16 is a cross-sectional view7of the reduced cross-section portion 136 of the catheter 100 taken along the broken line FIG. 16 - FIG. 16 shown in FIG. 11. FIG. 16 shows the outer layer 134 surrounding the substrate 132, the electrical traces 133. the tube 110, and the guide wire lumen 112 at the reduced cross-section portion 136 of the catheter 100.

[0096] The reduced cross-section portion 136 has a cross-sectional shape that is substantially circular. The reduced cross-section portion 136 has the smallest crosssection of the catheter 100. In some examples, the outer diameter of the reduced crosssection portion 136 is less than 0.023 inches such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0004 inches2. In some examples, the outer diameter of the reduced cross-section portion 136 is less than 0.022 inches such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0004 inches2. In some examples, the outer diameter of the reduced cross-sectionportion 136 is less than 0.020 inches, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0003 inches2.

[0097] FIG. 17 is a cross-sectional view of the transition portion 138 of the catheter 100 taken along the broken line FIG. 17 - FIG. 17 shown in FIG. 11. FIG. 17 shows the electrical wires 140 coupled to the substrate 132 to form an electrical connection with the electrical traces 133. Also, the proximal pressure sensor 142 is shown mounted on the substrate 132.

[0098] FIG. 18 is a cross-sectional view- of the catheter 100 taken along the broken line FIG. 18 - FIG. 18 shown in FIG. 11. FIG. 18 shows the electrical wires 140 inside the proximal shaft 148 proximate to the guide wire exit port 116 where the tube 110 terminates.

[0099] FIG. 19 is a cross-sectional view' of the catheter 100 taken along the broken line FIG. 19 - FIG. 19 shown in FIG. 11. FIG. 19 shows the electrical wires 140 inside the proximal shaft 148 after the tube 110 terminates. The electrical wires 140 can include eight wires for electrical power and communications transmission to and from the sensor assembly 106, and one additional twisted pair of wires connected to the proximal pressure sensor 142 for a total of ten wires. In some examples, the twisted pair of w ires connected to the proximal pressure sensor 142 are non-impedance controlled. The electrical wires 140 are sized to fit within the proximal shaft 148 and to be easily passed through a lumen of the proximal shaft 148 during device assembly.

[0100] The proximal shaft 148 remains within the guide catheter and is the most proximal portion of the catheter 100. In some instances, the proximal shaft 148 has an outside diameter of about 0.04 inches, a w all thickness of about 0.004 inches. The proximal shaft 148 can be manufactured from PEEK which provides axial and torsional stifftiess such that the proximal shaft 148 can be manipulated to reposition the distal end 102 of the catheter 100.

[0101] In some examples, the proximal shaft 148 can have a thinner wall thickness, for example from about 0.002 inches to about 0.003 inches, and can utilize a PEEK or non-PEEK material such as PEBAX or Polyurethane, and have a smaller outside diameter. The smaller outside diameter can be advantageous, as it will further reduce the likelihood of impeding fluid flow' w ithin the guide catheter, and in particular impeding contrast during a contrast die injection. In such examples, the proximal shaft 148 does not provide adequate stiffness by itself, but instead relies on the stiffness ofthe electrical wires 140 that are within the proximal shaft 148 to allow manipulation of the distal end 102 of the catheter 100 from outside the patient's body.

[0102] In yet further examples, the diameter (i.e., gage) of the electrical wires 140 is further reduced to less than 38 gage, and a stainless-steel stiffening member is included within the lumen of the proximal shaft 148 to provide the necessary stiffness to allow manipulation of the distal end 102 of the catheter 100 from outside the patient's body.

[0103] FIG. 20 schematically illustrates an example of a method 2000 of manufacturing the catheter 100. The catheter 100 is manufactured for insertion into a blood vessel for intravenous physiological and structural assessment such as by imaging a blood vessel and measuring blood pressure inside the blood vessel by having a reduced cross-section to mitigate influence on blood flow when the catheter 100 is positioned inside the blood vessel. By mitigating the influence on blood flow, the reduced cross-section of the catheter 100 improves the accuracy of the blood pressure measurements captured by the catheter 100.

[0104] The method 2000 includes an operation 2002 of obtaining the tube 110 having the guide wire lumen 112 for a guide wire. In some examples, the tube 110 is made of polyimide material. In some examples, the tube 110 can have an inner diameter of about 0.016 inches and a wall thickness of about 0.001 inches such that the tube 110 has an outside diameter of 0.018 inches. In some examples, the length L of the tube 1 10 is about 7 inches.

[0105] The method 2000 includes an operation 2004 of mounting the sensor assembly 106 on the tube 110. The sensor assembly 106 can include the ultrasound transducer array 124, the distal pressure sensor 126. several various sized and voltage rated capacitors, the plurality of ASICs 128, as well as other components, as discussed above.

[0106] The method 2000 includes an operation 2006 of mounting electrical conductors around the tube 110 for communicating electrical signals to and from the sensor assembly 106. In one example, operation 2006 includes plating one or more layers of conductive material onto an outside surface of the tube 110, and removing portions of the plating of the one or more layers of conductive material by etching or ablation to form the electrical traces 133 on the outside surface of the tube 110. In another example, operation 2006 includes printing one or more layers of conductive material on the outside surface of the tube 1 10 to form electrical traces 133 on theoutside surface of the tube 110. In another example, operation 2006 includes plating one or more layers of conductive material onto the substrate 132; removing portions of the plating of the one or more layers of conductive material by etching or ablation to form the electrical traces 133 on the substrate 132; and positioning the substrate 132 to surround the tube 110.

[0107] The method 2000 further includes an operation 2008 of applying the outer layer 134 around the electrical conductors. In some examples, the outer layer 134 is a heat shrink tubing that when applied causes the substrate 132 to surround the tube 110. In some examples, operation 2008 causes the reduced cross-section portion 136 of the catheter 100 to have a diameter that is 0.023 inches or less, such that the reduced crosssection portion 136 has a total cross-sectional area of about 0.0004 inches2. In some examples, operation 2008 causes the reduced cross-section portion 136 of the catheter 100 to have a diameter of 0.022 inches or less, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0004 inches2. In some further examples, operation 2008 causes the reduced cross-section portion 136 of the catheter 100 to have a diameter of 0.020 inches or less, such that the reduced cross-section portion 136 has a total cross-sectional area of about 0.0003 inches2.

[0108] The method 2000 can include an operation 2010 of attaching the electrical wires 140 to the electrical traces 133 at a proximal end of the tube 110 where the guide wire exit port 116 is located. In some examples, the proximal end 104 of the tube 110 extends about seven inches or more away from a distal end 102 of the tube 1 10. In further examples, the proximal end 104 of the tube 110 extends between nine and 10 inches away from the distal end 102 of the tube 110. In some examples, operation 2010 includes soldering, welding, or performing other connection techniques to attach the electrical wires 140 to the electrical traces 133.

[0109] FIG. 21 is a cross-sectional view of another example of a reduced crosssection portion 136a of the catheter 100. In this example, the reduced cross-section portion 136a includes the tube 110 defining the guide wire lumen 112. In this example, the tube 110 is made of a polymer material having embedded therein the electrical wires 140 that surround the guide wire lumen 112. The polymer material of the tube 110 in this example can include polyethylene, thermoplastic elastomer, or other type of polymer material. The electrical wires 140 that are embedded in the tube 110 are coupled to the sensor assembly 106.

[0110] The electrical wires 140 supply electrical power to the sensor assembly 106, and provide communications of electrical signals to and from the sensor assembly 106. Further, the electrical wires 140 provide structural integrity to the tube 110. In some examples, the electrical wires 140 enable the tube 110 to have a tensile strength at break greater than 3N when the tube 110 is made from a polymer that is not poly imide. [OHl] As shown in the example of FIG. 21, the electrical wires 140 include a total of eight wires. In some examples, three wires are configured for power transmission to the sensor assembly 106, and five wires are configured for communications transmission to and from the sensor assembly 106. Alternative quantities of wires can be embedded in the tube 110.

[0112] In this example, the tube 110 can have a wall thickness of about 0.003 inches, and the electrical wires can each have a diameter less than about 0.0025 inches (42 AWG). The guide wire lumen 112 has a diameter of about 0.016 inches to accommodate a guidewire having a diameter of about 0.014 inches. Accordingly, the reduced cross-section portion 136a of the catheter 100 can have a total outside diameter (OD) of about 0.022 inches, such that the reduced cross-section portion 136a has a total cross-sectional area of about 0.0004 inches2.

[0113] FIG. 22 is a cross-sectional view of another example of a reduced crosssection portion 136b of the catheter 100. In this example, the tube 110 includes electrical wires 140 that are embedded including eight wires with two sets of side-by- side wires 140a, 140b. The two sets of the side-by-side wires 140a, 140b are separated by a distance D. The four other wires of the eight w ires that are embedded in the tube 110 are separated by a second distance larger than the distance D between the wires in each set of the side-by-side wires 140a, 140b.

[0114] An electrical impedance of the two sets of side-by-side wires 140a and 140b is set based on the diameter of the wires, the separation distance D between the two wires, and the dielectric constant of the polymer material of the tube 110 encapsulating the wires. In some examples, the two sets of side-by-side wires 140a and 140b have a designed nominal impedance between about 80 ohms and about 116 ohms. In some examples, the tw o sets of side-by-side wires 140a and 140b have a designed nominal impedance of about 93 ohms.

[0115] As previously discussed, pressure ratios are utilized to determine when an intervention is warranted and when an intervention can be safely deferred. There are two types of pressure ratios that are typically used. Fractional Flow' Reserve (FFR),which is a whole cycle pressure ratio measured when the heart is at maximum hyperemia, and a resting or non-hyperemic pressure ratio measured during the end diastolic period of the cardiac cycle.

[0116] FFR procedures typically utilize intracoronary (IC) or intravascular (IV) adenosine to achieve maximum hyperemia. The administration of adenosine adds cost and time to the procedure and may create patient discomfort. An FFR pressure ratio (Pressure Distal (PD) / Pressure Aortic (PA) threshold of 0.80 has been established to guide interventional decision making. There is a growing body of clinical evidence supporting FFR guided revascularization. The use of FFR to guide revascularization decisions is now a class 1 A recommendation.

[0117] Resting pressure ratios are non-hyperemic and do not require the administration of adenosine, thereby reducing cost, procedure time, and patient discomfort. Consequently, resting pressure ratios have become the most common technique to guide revascularization decision making. It is estimated that the FFR and the resting pressure ratio techniques disagree about whether to intervene or not about 20% of the time. For example, when FFR is less than 0.80 and resting pressure ratios are greater than 0.89, there is approximately a 20% discordance between FFR and resting pressure ratios. Most of the discordance occurs when the resting pressure ratio is between 0.86 to 0.92. Given the foregoing, it would be useful to have a new technique to provide additional guidance on whether to recommend an intervention or not.

[0118] FIG. 23 schematically illustrates an example of a method 2300 of determining when to perform an in ten ention using the catheter 100. The method 2300 includes determining a pressure ratio that can be used to guide revascularization decision making such as when there is discordance between FFR and resting pressure ratios. The method 2300 uses the diameter of the sensor assembly 106 to calculate the pressure ratio that can be compared to a threshold for determining whether a lesion is flow limiting and warrants an intervention. The pressure ratio is measured when the sensor assembly 106 partially occludes a blood vessel. As described above, the sensor assembly 106 can have a diameter of about 0.043 inches.

[0119] The method 2300 includes an operation 2302 of capturing a first pressure reading by the distal pressure sensor 126 when the sensor assembly 106 is positioned across a region of interest such as a suspected lesion or occlusion. The region of interest will typically have a narrower inside diameter than other healthy portions of theblood vessel. The diameter of the sensor assembly 106 at least partially obstructs blood flow through the region of interest which influences the first pressure reading captured by the distal pressure sensor 126.

[0120] The method 2300 includes an operation 2304 of capturing a second pressure reading by the proximal pressure sensor 142 while the sensor assembly 106 is positioned across the region of interest such as the suspected lesion or occlusion.Operation 2304 occurs concurrently or substantially at the same time as operation 2302. In operation 2304, the proximal pressure sensor 142 captures the second pressure reading when the proximal pressure sensor 142 is positioned proximally to normal, health, and / or non-occluded portion of the blood vessel or within the guide catheter.

[0121] The method 2300 includes an operation 2306 of calculating a pressure ratio between the first pressure reading captured in operation 2302 versus the second pressure reading captured in operation 2304. When stenosis or occlusion in the region of interest is limited or non-existent, the pressure ratio will be close to 1 : 1 because the diameter of the sensor assembly 106 will have less influence on the first pressure reading when there is a limited amount of stenosis or occlusion. In contrast, when stenosis or occlusion is present in the region of interest, the pressure ratio will be different from 1 : 1 because the diameter of the sensor assembly 106 will have a larger influence on the first pressure reading when stenosis or occlusion is present.Accordingly, by having the sensor assembly 106 positioned across the region of interest during capture of both the first and second present readings, the ratio calculated in operation 2306 can have a higher sensitivity than the resting pressure ratios that are typically calculated when the reduced cross-section portion 136 is positioned across the region of interest because the diameter of the sensor assembly 106 causes a larger difference between the first pressure reading and the second pressure reading when there is stenosis or occlusion in the region of interest.

[0122] The method 2300 includes an operation 2308 of determining whether the pressure ratio calculated in operation 2306 is equal to or less than a predetermined threshold. The predetermined threshold is lower than the thresholds typically used for FFR and resting pressure ratios in view of the higher sensitivity7of pressure ratio calculated in operation 2306 due to the partial obstruction caused by the sensor assembly 106 across the region of interest.

[0123] When the pressure ratio calculated in operation 2306 is above the predetermined threshold (i. e. , “No” in operation 2308), the method 2300 can proceed toan operation 2310 of recommending no intervention because stenosis or occlusion is likely limited or not present in the region of interest since the pressure ratio is close to 1: 1. When the pressure ratio calculated in operation 2306 is equal to or less than the predetermined threshold (i.e., “Yes” in operation 2308), the method 2300 can proceed to an operation 2312 of recommending intervention because stenosis or occlusion is likely present in the region of interest.

[0124] The pressure ratio calculated in the method 2300 utilizes the obstructive nature of the sensor assembly 106 positioned across a suspected lesion, and may be used to improve the accuracy of clinical decisions on whether to intervene or not. The method 2300 provides several advantages over fractional flow reserve (FFR). For example, the method 2300 eliminates cost and time associated with administering a medication to achieve coronary vasodilation or hyperemia such as adenosine, and also eliminates the associated patient discomfort from being placed in a state of hyperemia which is necessary to perform the FFR technique. Further, the method 2300 can remove ambiguities or discordance between FFR and the resting pressure ratios that are typically calculated to determine whether an intervention is necessary or not.

[0125] The sensor assembly 106 has a known cross-sectional area (e.g., about 0.0015 inches2from a diameter of about 0.043 inches) that provides a known obstruction to the normal flow of blood across a region of interest. The addition of the known obstruction within a narrowing of a blood vessel can result in further separation of the distal pressure (i.e., captured by the distal pressure sensor 126) compared to the aortic pressure (i.e., the proximal pressure captured by the proximal pressure sensor 142). The further separation between the distal and proximal pressures may overcome challenges associated with detecting small changes in the pressure ratio. Thus, the pressure ratio used in the method 2300, which is caused by the known obstruction of the sensor assembly 106, may have a higher sensitivity than resting and hyperemia blood pressure ratios calculated across either a partial or whole cardiac cycle.

[0126] Additionally, the pressure ratio used in the method 2300 can benefit from a minimal luminal area and percent of plaque burden that can be automatically and continuously calculated based on the IVUS imaging of the ultrasound transducer array 124. The continuous calculation of the minimum luminal area and the percent of plaque burden can be combined with the pressure ratio calculated from the pressure readings captured by the distal pressure sensor 126 and the proximal pressure sensor 142 during use of the catheter 100 to assess w hether to recommend intervention or deferintervention. Advantageously, the catheter 100 is a single device that can be used to measure and / or calculate pressure ratios based on distal and proximal pressure readings, minimal luminal area, and percent plaque burden to improve clinical decision making with regards to whether an intervention is needed, or not.

[0127] FIG. 24 is an isometric view of the distal end 102 of another example embodiment of the catheter 100 for intravenous physiological and structural assessment. FIG. 25 is an isometric view of the distal end 102 of the example embodiment of the catheter 100 shown in FIG. 24 with the distal tip 120 shown in phantom. FIG. 26 is a cross-sectional isometric view of the distal end 102 of the example embodiment of the catheter 100 of FIG. 24. As shown in FIGS. 24-26, the distal pressure sensor 126 is located on the distal tip 120 of the catheter 100 such that the distal pressure sensor 126 is positioned downstream of the sensor assembly 106. For example, the distal pressure sensor 126 is positioned forward or distal of the ultrasound transducer array 124.

[0128] By positioning the distal pressure sensor 126 distal of the ultrasound transducer array 124, the pressure readings are captured distal of a region of interest (e g., where a lesion or occlusion is suspected) while the ultrasound transducer array 124 is positioned across the region of interest for imaging the region of interest. This configuration may be beneficial as pressure readings are captured distal to a luminal narrowing while imaging is performed at the luminal narrowing to determine the minimal luminal area and percent of plaque burden.

[0129] In the example shown in FIG. 25, a connector 129 is electrically terminated at a first end to the sensor assembly 106 and is electrically terminated at an opposite, second end to the distal pressure sensor 126. This allows the first end of the connector 129 to be connected to the same electrical landing pads on the sensor assembly 106 used to connect the distal pressure sensor 126 to the sensor assembly 106 in the example embodiments of FIGS. 1-22. The connector 129 can include a flexible substrate. In some examples, the flexible substrate is about 12.5 pm thick and includes traces that communicatively connect the distal pressure sensor 126 to the sensor assembly 106. Alternatively, the connector 129 can include one or more wires, cables, and the like. In some alternative examples, the distal pressure sensor 126 is communicatively coupled to the sensor assembly 106 via a wireless connection such that the connector 129 is not used to physically connect the distal pressure sensor 126 to the sensor assembly 106.

[0130] As shown in FIGS. 24 and 26, the distal tip 120 includes an aperture 127 to expose the distal pressure sensor 126 to blood flow when the catheter 100 is inserted inside a blood vessel. The distal tip 120 can be made of a soft polymer low-temperature reflowable material such as perfluoroalkoxy alkanes (PF A), or like material. The distal pressure sensor 126 can be embedded into the distal tip 120, and thereafter, the aperture 127 can be formed such as by using a laser scalpel to remove a portion of the distal tip 120 to expose the distal pressure sensor 126. In alternative examples, the aperture 127 can be formed into the distal tip 120 such as by using a mold to shape the distal tip 120 to include the aperture 127. In the example embodiment of FIGS. 24-26, the distal tip can include an extended length to accommodate the distal pressure sensor 126. For example, the distal tip 120 can have a length of about 1.5 cm or longer. In contrast, the distal tip 120 in the example embodiments of FIGS. 1-22 can have a length of about 1.0 cm.

[0131] The various examples described above are provided by way of illustration only and should not be construed to be limiting in any way. Various modifications can be made to the examples described above without departing from the true spirit and scope of the disclosure.

Claims

What is claimed is:

1. A catheter for intravenous physiological and structural assessment, the catheter comprising: a tube defining a guide wire lumen; a sensor assembly mounted on the tube, the sensor assembly including: an ultrasound transducer array; and a pressure sensor; electrical conductors positioned around the tube for communicating electrical signals to and from the sensor assembly; and an outer layer surrounding the electrical conductors, wherein a cross-section of the catheter including the tube, the electrical conductors, and the outer layer has a diameter of 0.023 inches or less.

2. The catheter of claim 1, wherein the electrical conductors include a plating of one or more layers of conductive material on an outside surface of the tube, and portions of the plating of the one or more layers of conductive material are removed by etching or ablation to form electrical traces on the outside surface of the tube.

3. The catheter of claim 1. wherein the electrical conductors include one or more layers of conductive material printed on an outside surface of the tube to form electrical traces on the outside surface of the tube.

4. The catheter of claim 1, wherein the electrical conductors include a substrate having a plating of one or more layers of conductive material with portions of the plating of the one or more layers of conductive material removed by etching or ablation to form electrical traces on the substrate, and wherein the substrate is shaped to surround the tube.

5. The catheter of any of the preceding claims, wherein the tube is made of polyimide having an inner diameter of 0.016 inches and a wall thickness of 0.001 inches.

6. The catheter of any of the preceding claims, wherein the tube extends between a guide wire entry port and a guide wire exit port, and wherein a length between the guide wire entry port and the guide wire exit port is seven inches or more.

7. The catheter of claim 6, further comprising: electrical wires coupled to the electrical traces proximate the guide wire exit port.

8. The catheter of any of claims 2-7, wherein the electrical traces include three traces configured for power transmission and five traces configured for communications transmission.

9. The catheter of claim 8, further comprising: a second pressure sensor mounted under the outer layer toward the guide wire exit port; and an aperture formed in the outer layer for exposing the second pressure sensor to fluids.

10. The catheter of claim 8, wherein the tube has a beveled edge at the guide wire entry port.

11. The catheter of any of the preceding claims, wherein the outer layer is a heat shrink tubing.

12. The catheter of any of the preceding claims, wherein the diameter of the crosssection of the catheter including the tube, the electrical conductors, and the outer layer is 0.020 inches or less.

13. The catheter of any of the preceding claims, wherein the pressure sensor is positioned distally of the ultrasound transducer array.

14. A method of manufacturing a catheter for insertion into a blood vessel, the method comprising: obtaining a tube having a lumen for a guide wire;mounting a sensor assembly on the tube, the sensor assembly including an ultrasound transducer array and a pressure sensor; mounting electrical conductors around the tube for communicating electrical signals to and from the sensor assembly; and applying an outer layer around the electrical conductors, wherein a cross-section of the catheter including the tube, the electrical conductors, and the outer layer is 0.023 inches or less.

15. The method of claim 14, wherein the electrical conductors are mounted around the tube by: plating one or more layers of conductive material onto an outside surface of the tube; and removing portions of the plating of the one or more layers of conductive material by etching or ablation to form electrical traces on the outside surface of the tube.

16. The method of claim 14, wherein the electrical conductors are mounted around the tube by: printing one or more layers of conductive material on an outside surface of the tube to form electrical traces on the outside surface of the tube.

17. The method of claim 14, wherein the electrical conductors are positioned around the tube by: plating one or more layers of conductive material onto a substrate; removing portions of the plating of the one or more layers of conductive material by etching or ablation to form electrical traces on the substrate; and positioning the substrate to surround the tube.

18. The method of claim 17. wherein the outer layer is a heat shrink tubing that when applied causes the substrate to surround the tube.

19. The method of any of claims 15-18, further comprising:ataching electrical wires to the electrical traces at a proximal end of the tube, the proximal end of the tube extending seven inches or more away from a distal end of the tube.

20. The method of any of claims 14-19, wherein the tube is made of polyimide having an inner diameter of 0.016 inches and a wall thickness of 0.001 inches.

21. A catheter for intravenous physiological and structural assessment, the catheter comprising: a tube defining a guide wire lumen, the tube made of a polymer material having embedded therein wires that surround the guide wire lumen, the tube having a wall thickness of 0.003 inches, and the wires each having a diameter less than 0.0025 inches; and a sensor assembly mounted on the tube, the sensor assembly coupled to the wires embedded in the tube for communicating electrical signals to and from the sensor assembly, and the sensor assembly including: an ultrasound transducer array; and a pressure sensor.

22. The catheter of claim 21, wherein the tube has an inner diameter of 0.016 inches.

23. The catheter of claim 21 or 22, wherein the tube extends between a guide wire entry port and a guide wire exit port, and the tube has a length of seven inches or more between the guide wire entry port and the guide wire exit port.

24. The catheter of claim 23, further comprising: a second pressure sensor mounted under the outer layer toward the guide wire exit port; and an aperture formed in the outer layer for exposing the second pressure sensor to fluids.

25. The catheter of any of claims 21-24, wherein the wires include three wires configured for power transmission and five wires configured for communications transmission.

26. The catheter of any of claims 21-25. wherein the polymer material is polyethylene or a thermoplastic elastomer.

27. The catheter of any of claims 21-26, wherein the wires embedded in the tube are evenly spaced apart.

28. The catheter of any of claims 21-26, wherein the wires embedded in the tube include two sets of side-by-side wires, the w ires in each set of the side-by-side wires is separated by a distance, and wherein an electrical impedance of the wires in each set of the side-by-side wires is based on a diameter of the wires, the distance, and a dielectric constant of the tube.

29. The catheter of claim 28, wherein the tube includes eight wires, with four wires of the eight wires being separated by a second distance larger than the distance between the wires in each set of the side-by-side wires.

30. A method of determining when to perform an intervention inside a blood vessel, the method comprising: capturing a first pressure reading using a distal pressure sensor when a sensor assembly is positioned across a region of interest; capturing a second pressure reading using a proximal pressure sensor when the sensor assembly remains positioned across the region of interest; calculating a pressure ratio between the first pressure reading and the second pressure reading; comparing the pressure ratio to a threshold; and recommending the intervention when the pressure ratio is less than the threshold.

31. The method of claim 30, wherein the sensor assembly has a diameter of about 0.043 inches.

32. The method of claim 30. wherein the distal pressure sensor is positioned distally of the sensor assembly.

33. The method of claim 30. further comprising: calculating a minimal luminal area based on imaging captured by an ultrasound transducer array on the sensor assembly; and determining whether to intervene or not based on the pressure ratio in combination with the minimal luminal area.

34. The method of claim 33, wherein the distal pressure sensor is positioned distally of the ultrasound transducer array.

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