Methods and systems for optimizing perivascular neuromodulation therapy using computational fluid dynamics

Abstract

Methods and systems for optimizing perivascular neuromodulation therapy using computational fluid dynamics. Digital data related to three-dimensional imaging of a target vessel and corresponding hemodynamic data are inputs for generating a computational fluid dynamics (CFD) model. The CFD model enables identification of one or more regions of the vessel suitable for neuromodulation therapy and / or identification of one or more regions of the vessel to be avoided during therapy. Systems of the present technology may include a neuromodulation catheter, a computing device that can generate and analyze the CFD model, and a user interface for displaying the vessel with markers for target regions and / or avoidance regions.

Description

[0001] This application is a divisional application of an invention patent application with an international application date of 2017 / 10 / 27, international application number PCT / US2017 / 058731, and application number 201780081286.2 entering the Chinese national phase, entitled "Methods and systems for optimizing perivascular nerve modulation therapy using computational fluid dynamics."

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Non-Provisional Patent Application No. 15 / 337,742, filed October 28, 2016, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0004] The present technology relates to perivascular neuromodulation. In particular, various embodiments of the present technology relate to methods and systems for informed decision making regarding whether to deliver neuromodulation therapy to various regions of a target vessel. Background Art

[0005] The sympathetic nervous system (SNS) is the main involuntary body control system that is usually associated with stress response. The fibers of SNS extend through the tissue in almost every organ system of human body and can affect characteristics such as pupil diameter, intestinal motility and urine output. This regulation can be adaptively used to maintain homeostasis or to prepare the body to make a rapid response to environmental factors. However, the chronic activation of SNS is a common maladaptive reaction that can drive the evolution of many disease states. In particular, the excessive activation of kidney SNS has been experimentally and in humans identified as a possible contributor to the complex pathophysiology of hypertension, the state of volume overload (such as, heart failure) and progressive nephropathy.

[0006] The sympathetic nerves of the kidney terminate in the renal blood vessels, juxtaglomerular apparatus, and renal tubules and other structures. For example, stimulation of the renal sympathetic nerves can cause increased renin release, increased sodium reabsorption, and reduced renal blood flow (blood flow). These and other neural regulatory components of renal function are significantly stimulated in the disease states characterized by elevated sympathetic tone. For example, as a result of renal sympathetic nerve efferent stimulation, reduced renal blood flow and glomerular filtration rate are likely to be the basis of renal function loss (i.e., renal insufficiency due to the progressive complications of chronic heart failure) in cardiorenal syndrome. Pharmacological strategies for hindering the results of renal sympathetic nerve stimulation include centrally acting sympathetic drugs, beta blockers (e.g., to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (e.g., to prevent angiotensin II and aldosterone activation after renin release) and diuretics (e.g., to antagonize sodium and water retention (retention) mediated by renal sympathetic nerves). However, these pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects, and others. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Many aspects of the present technology may be better understood by reference to the following drawings. The components in these drawings are not necessarily to scale. Instead, emphasis is placed on clearly illustrating the principles of the present technology. For ease of reference, the same reference numerals may be used throughout this disclosure to identify identical or at least generally similar or analogous components or features.

[0008] Figure 1 is a block diagram illustrating a method for evaluating blood vessels for neuromodulation therapy based on a computational fluid dynamics (CFD) model in accordance with an embodiment of the present technology.

[0009] Figure 2 is a partial schematic diagram of a neuromodulation system configured according to an embodiment of the present technology.

[0010] Figure 3 yes Figure 2 Side view of the distal portion of a neuromodulation catheter positioned within a blood vessel.

[0011] Figure 4 is a graphical representation of a computational fluid dynamics model of a blood vessel in accordance with an embodiment of the present technology.

[0012] Figure 5 is a partial schematic diagram of a neuromodulation system configured according to another embodiment of the present technology.

[0013] Figure 6 yes Figure 5 Side view of the distal portion of a neuromodulation catheter and sensing guidewire positioned within a blood vessel.

[0014] Figure 7-9 Anatomical and conceptual side, cross-sectional, and magnified views of blood vessels illustrating various physiological and pathological features.

[0015] Figure 10 Modulation of renal nerves using the neuromodulation catheters described herein is shown in accordance with additional embodiments of the present technology.

[0016] Figure 11 is a block diagram showing an overview of a device on which some embodiments of the present technology may operate.

[0017] Figure 12 is a block diagram illustrating an overview of an environment in which some embodiments of the present technology may operate.

[0018] Figure 13 A conceptual illustration of the sympathetic nervous system (SNS) and how the brain communicates with the body via the SNS.

[0019] Figure 14 is an enlarged anatomical illustration of the nerves innervating the left kidney to form the renal plexus surrounding the left renal artery.

[0020] Figure 15 and Figure 16 Anatomical and conceptual views of the human body depicting efferent and afferent neural communication between the brain and kidneys, respectively.

[0021] Figure 17 and Figure 18 These are anatomical diagrams of the human arterial and venous vascular systems, respectively. DETAILED DESCRIPTION

[0022] Methods and systems according to embodiments of the present technology can be configured to: detect hemodynamic parameters of a patient's blood vessels, generate one or more models of the blood vessels, and analyze regions of the blood vessels to inform decision making regarding potential regions for delivering neuromodulation therapy. Regions of the blood vessels can be identified for delivery of therapy (e.g., target regions), while other regions can be identified as unsuitable for therapy (e.g., avoidance regions). Figure 1-18 Specific details of several embodiments of the present technology are described. Although many embodiments are described with respect to devices, systems, and methods for catheter-based perivascular renal neuromodulation, other applications and other embodiments beyond those described herein are also within the scope of the present technology. For example, at least some embodiments of the present technology may be used for intraluminal neuromodulation, extravascular neuromodulation, non-renal neuromodulation, and / or for treatments other than neuromodulation.

[0023] It should be noted that other embodiments besides those disclosed herein are within the scope of the present technology. Furthermore, embodiments of the present technology may have configurations, components, and / or processes that are different from those shown or described herein. Furthermore, one of ordinary skill in the art will understand that embodiments of the present technology may have configurations, components, and / or processes other than those shown or described herein, and that these and other embodiments may not have some of the configurations, components, and / or processes shown or described herein without departing from the present technology.

[0024] As used herein, the terms "distal" and "proximal" define a position or direction relative to a clinician or clinician's control device (e.g., a handle of a neuromodulation catheter). The terms "distal" and "distally" refer to a position along the length of the device that is away from the clinician or clinician's control device or in a direction away from the clinician or clinician's control device. The terms "proximal" and "proximally" refer to a position along the length of the device that is close to the clinician or clinician's control device or in a direction toward the clinician or clinician's control device. The headings provided herein are for convenience only and should not be construed as limiting the disclosed subject matter.

[0025] I. Selected Embodiments of Systems and Associated Methods for Evaluating Vasculature for Neuromodulation Therapy

[0026] Renal perivascular neuromodulation therapy is intended to regulate the autonomic nervous system, particularly the SNS, by modulating or disrupting renal efferent sympathetic nerves and afferent renal sensory nerves. However, delivering neuromodulation therapy at locations in a blood vessel with localized flow anomalies and / or secondary flow areas increases the risk that the patient may experience undesirable events in response to the therapy. Localized flow anomalies and / or secondary flow areas cannot be seen using traditional vascular imaging methods (such as fluoroscopy). Therefore, patients may benefit from methods and systems configured to display or otherwise notify a user (e.g., a clinician) of locations in a target blood vessel with localized flow anomalies and / or secondary flow areas. In this way, clinicians can reduce the risk of undesirable events by avoiding delivering neuromodulation therapy at these locations. The present technology includes several embodiments of methods and systems for avoiding delivering neuromodulation therapy to locations in a blood vessel with localized flow anomalies and / or secondary flow areas. These methods and systems are configured to provide visual, auditory, and / or tactile feedback to guide the positioning of the neuromodulation catheter 210 at one or more suitable treatment locations in the patient's blood vessel.

[0027] Figure 11 is a block diagram illustrating a method 100 for evaluating blood vessels for delivering neuromodulation therapy based on a computational fluid dynamics (CFD) model according to an embodiment of the present technology. Figure 1 As shown in FIG, method 100 includes receiving, at a processor, digital three-dimensional imaging data related to a blood vessel (block 110). The three-dimensional imaging data of the blood vessel can represent a renal artery, a pulmonary artery, a hepatic artery, a coronary artery, an aorta, and / or other blood vessels suitable for neuromodulation therapy. In some embodiments, the blood vessel can be a main blood vessel (e.g., a renal artery), at least one branch vessel of the main blood vessel (e.g., a posterior branch or an anterior branch of the renal artery), at least one accessory blood vessel directly coupled to the branch vessel (e.g., an inferior anterior segmental artery or an inner segmental artery), or another blood vessel coupled to the main blood vessel (e.g., the aorta), and / or combinations thereof. The digital three-dimensional imaging data may be generated in part using input from one or more of the following modalities: angiography (e.g., X-ray, single view, multi-view, computed tomography, positron emission, single positron emission), ultrasound, digital X-ray (e.g., contrast), digital fluoroscopy, magnetic resonance imaging (MRI) (e.g., contrast or non-contrast), computed tomography (CT) (e.g., spiral, helical, dual source), and / or a modality otherwise suitable for generating three-dimensional imaging input in a digital format. The three-dimensional imaging data may include information related to one or more features of a vessel. For example, the information may include data corresponding to at least one dimension of a vessel feature, such as a cross-sectional area, a cross-sectional diameter, a volume, a length, and / or a combination thereof. In other embodiments, the feature may be a vessel wall or portion thereof (e.g., adventitia, media, and intima), a lumen, a branch, a bifurcation, a carina, an ostium, a tapered region, an aneurysm, fibromuscular dysplasia, an occlusion, an impingement, a calcification, an intimal deposit, and / or a combination thereof. Figure 7-9 These features are described in detail.

[0028] In addition to receiving the three-dimensional imaging data at the processor, method 100 also includes receiving hemodynamic data associated with the vascular sensor (block 120). For example, the received hemodynamic data can be measurements of blood pressure, blood flow, blood impedance, viscosity of the patient's blood, other hemodynamic parameters, and / or combinations thereof. The received hemodynamic data can be based on measurements taken inside the blood vessel, outside the blood vessel, outside the patient's body, and / or combinations thereof. Blood viscosity can be assumed or measured. For example, assuming a blood viscosity of 3×10 -3 to 4×10 -3 Pascal-second (e.g., similar to water).

[0029] Blood pressure data, blood flow data, blood impedance data, and / or combinations thereof can be measured by one or more sensors, such as sensors coupled to a neuromodulation catheter positioned in a target vessel according to the present technology. In some embodiments, method 100 includes coupling a sensor to a patient to detect and record data corresponding to one or more hemodynamic parameters before or during intravascular treatment. The sensor can be an external device coupled to the patient, for example, positioned near the patient's vessel. For example, the sensor can be an external pressure cuff, a Doppler ultrasound flowmeter, a magnetic resonance imaging (MRI) machine, and / or a combination thereof. The sensor can alternatively be an internal device positioned within the patient's body, such as delivered transluminally into the patient's vessel. For example, the sensor can be coupled to a neuromodulation catheter 210, which can be delivered transluminally into the vessel. A transluminally delivered neuromodulation catheter can be positioned within a portion of the patient's vessel having laminar flow and / or otherwise positioned to perform measurements of one or more hemodynamic parameters. The sensor can include, for example, a blood flow sensor, a blood pressure sensor, a blood impedance sensor, and / or a combination thereof. For example, the sensor can be a combination blood pressure and blood flow sensor carried by a guidewire (e.g., the blood pressure and blood flow sensor(s) can be the same sensor or different sensors located on the same guidewire), such as a fractional flow reserve (FFR) guidewire. In some embodiments, the combination guidewire also includes a transducer. In some embodiments, method 100 can include coupling more than one sensor to the patient.

[0030] Several embodiments of method 100 include measuring blood flow, blood pressure, and / or blood impedance in a main portion of a blood vessel (e.g., a renal artery) and / or branches of the main artery (e.g., anterior and / or posterior branches of the renal artery). The measurements can be performed in a portion of the main vessel or its branches with stable (e.g., laminar) flow, a portion with unstable (e.g., turbulent, changing, secondary) flow, and / or a combination thereof.

[0031] After receiving the hemodynamic data, method 100 continues by generating a computational fluid dynamics (CFD) model or representation of the target vessel based at least in part on the three-dimensional imaging data of the vessel (block 110) and the hemodynamic data (block 120). Using equations, algorithms, and various statistical methods, information related to the three-dimensional imaging data of the vessel (e.g., vessel geometry) and hemodynamic data (e.g., blood pressure, blood flow, blood impedance, and / or blood viscosity) can be used to generate a CFD model of the vessel. The CFD model can be generated using a CFD workflow or other suitable method for generating a CFD representation. The CFD workflow begins by creating a volume mesh that is aligned with certain features (e.g., geometry) of the vessel represented by the three-dimensional imaging data. The hemodynamic data (e.g., blood flow data and / or blood pressure data) can be used to form one or more boundary conditions (e.g., inlets) for the CFD simulation in the CFD workflow. The CFD workflow can generate a flow field, and if more than one CFD model is generated (e.g., a different CFD model can be generated for a portion of a vessel), the CFD models can be coupled (e.g., at the outlet) to enable calculation of a blood flow / blood pressure relationship. In some embodiments, the blood pressure data can be a proximal boundary condition, and each outlet (e.g., a distal boundary) can be coupled to a zero-dimensional representation of the blood impedance, resistance, and compliance / capacitance of the patient's circulation distal to the boundary. The CFD model can be displayed using one resolution in the image or multiple resolutions in a single representation. For example, a first portion of the CFD model can have a lower resolution than a second portion. It is expected that using a lower resolution in the first portion will reduce the duration of calculating certain parameters, so that a CFD model with at least two resolutions can be generated faster than a CFD model with a resolution across the second portion displayed across the CFD model. In some embodiments, the CFD model can be validated using a suitable validation method (e.g., invasive measurements).

[0032] A user (e.g., a clinician) and / or a computer can form certain assumptions regarding one or more characteristics of vascular physiology and hemodynamics or other information input into the CFD model. For example, an assumption can be that blood behaves as an incompressible fluid and / or that regions (e.g., segmented regions) of a vessel have rigid walls. In some embodiments, one or more hemodynamic parameters can be derived from empirical data, conglomerate data, and / or a combination thereof. In these embodiments, a CFD model of a vessel can be generated, in part, by applying one or more hemodynamic parameters derived from the empirical or conglomerate data to a CFD workflow. The empirical data can be obtained from a population database generated by a user or another group. The population database can include blood pressure data and / or blood flow data, each of which can be generalized. For example, the generalized blood pressure can be 120 / 80 mmHg, and the generalized blood flow can be 500 ml / min. In other embodiments, the CFD representation can include sample waveforms (e.g., measured, calculated, or standardized) using calculation methods such as ensemble averaging.

[0033] The CFD model is expected to facilitate the characterization and display of traditionally difficult-to-measure physiological and pathological parameters of the entire vessel being targeted for perivascular denervation. The CFD model is expected to use anatomically accurate geometry and vasodynamically accurate vascular inputs to quickly and accurately provide information about the vessel. Iterative processing of the CFD model can achieve convergence with respect to physiological and pathological aspects of the modeled vessel(s). Measuring vessel wall shear stress ("WSS") is difficult and invasive without a CFD model, which can map the spatial distribution of WSS, one of several physiological characteristics that may be desirable to avoid when delivering neuromodulation therapy.

[0034] Based on the CFD model generated by the processor (block 130), method 100 may continue by identifying, using the processor, target regions and / or avoidance regions of the vessel for delivering neuromodulation therapy (block 140). The locations of the avoidance regions may be identified on the CFD model by the processor using equations, algorithms, various statistical methods, and / or analysis of the patient's anatomical features, by user observation, and / or by a combination thereof. The avoidance regions may be one or more regions of the vessel having localized flow anomalies, physiological characteristics, and / or pathological characteristics (e.g., disease) (collectively, "flow anomalies"). In some embodiments, flow anomalies are associated with an increased risk of undesirable events following neuromodulation therapy. Localized flow anomalies may include, but are not limited to, secondary flow (e.g., turbulence, flow separation, and vortex formation), flow shocks, regions of low WSS, high WSS, and / or WSS gradients. The avoidance regions may include one or more pathological characteristics of vascular disease (e.g., calcification, fibromuscular dysplasia, aneurysm), and / or one or more physiological characteristics of the vessel (e.g., ostia, carina, tapered region, bifurcation), and / or combinations thereof. In other embodiments (not shown), method 100 may include identifying, via the processor, a target region of a vessel suitable for neuromodulation therapy. For example, the target region may be one or more regions of a vessel that lack localized flow abnormalities, physiological characteristics, and / or pathological characteristics associated with an increased risk of an undesirable event following neuromodulation therapy.

[0035] A target region can be identified by determining whether a measured value of a hemodynamic parameter at a given location is within a "normal" range or above / below a value of the hemodynamic parameter that indicates the absence of localized flow anomalies and / or secondary flow regions (e.g., a threshold hemodynamic parameter). For example, if the hemodynamic parameter is blood pressure, a blood pressure value within a "normal" range for blood pressure at a given location can trigger a recommendation to deliver neuromodulation therapy at the given location (e.g., a target region). Similarly, an avoidance region can be identified by determining whether a measured value of a hemodynamic parameter at a given location is outside a "normal" range or below / above a value of the hemodynamic parameter that indicates localized flow anomalies and / or secondary flow regions. For example, a blood pressure value outside a "normal" range for blood pressure at a given location can trigger a recommendation to avoid delivering neuromodulation therapy at the given location (e.g., an avoidance region). Each corresponding threshold hemodynamic parameter can be determined using empirical data, synthetic data, or other suitable data useful for establishing threshold hemodynamic parameters. For example, threshold hemodynamic parameters can be determined for blood flow, blood pressure, blood impedance, and / or other hemodynamic parameters using the methods described herein.

[0036] Method 100 can use an algorithm executed by a processor to compare one or more hemodynamic parameters to one or more threshold hemodynamic parameters. The threshold hemodynamic parameters can be predetermined, or the threshold hemodynamic parameters can be calculated before performing the comparison. In some embodiments, the processor that analyzes the hemodynamic parameters can include an algorithm that removes any significantly irregular hemodynamic parameter(s) to automatically correct the anomaly. In other embodiments, the comparison between one or more hemodynamic parameters and one or more threshold hemodynamic parameters can be performed by a user, a system, a device, and / or a combination thereof. In further embodiments, the algorithm can use two or more hemodynamic parameters and / or other data to provide a combined hemodynamic parameter that is more closely associated with a target and / or avoidance region that identifies a vessel than any one of the individual hemodynamic parameters alone.

[0037] Method 100 optionally continues by displaying a representation of the blood vessel on a user interface (block 150), the representation of the blood vessel including visual markers indicating one or more avoidance regions not to be used for delivering neuromodulation therapy. Figure 4and the corresponding description below. In some embodiments (not shown), the displayed representation may also include markings of one or more target areas of the vessel for delivering neuromodulation therapy. In other embodiments, the representation may display more than one portion of the vessel, such as a first portion and a second portion. The first portion and the second portion may be continuous or separate (e.g., different portions separate the first portion from the second portion). The displayed first portion may correspond to one or more areas suitable for delivering neuromodulation therapy (e.g., target areas), while the displayed second portion may correspond to one or more avoidance areas for avoiding delivery of neuromodulation therapy. Different resolutions may be used to display different features of the representation. Each of the avoidance areas and the target area may be visually displayed on the representation using unique corresponding markings such as color, shading, pattern, shape, and / or a combination thereof. For example, the avoidance area may be displayed on the representation using a red circle (e.g., a red circle) encompassing the avoidance area, while the target area may be displayed using a green circle (e.g., a green circle) surrounding the target area. Similarly, the avoidance area may be displayed using a shape with a red gradient, where the center of the avoidance area is colored dark red and the sides are colored light red. Similarly, a green gradient colored shape can be used to display the target area. In some embodiments, a yellow circle with a solid color or gradient color (e.g., a yellow circle) can be used to cover potential vascular treatments for which there is no data or uncertain data. In other embodiments, different colors, patterns, and shapes (e.g., arrows) can be displayed to indicate avoidance areas, target areas, and potential areas. The CFD model information thus provided to the clinician can be used to optimize the neuromodulation process.

[0038] With reference to the vascular assessment results displayed on the user interface, the clinician can deliver the neuromodulation catheter 210 to the patient's blood vessel while monitoring the position of the catheter within the blood vessel. Figure 10 Described in more detail, a neuromodulation catheter can be delivered to a patient's blood vessel using the methods described herein according to the present technology or alternatively using other methods suitable for delivery catheters. For example, the position of a portion of a neuromodulation catheter (e.g., a neuromodulation component 230) can be monitored while the catheter is being positioned within a blood vessel. In some embodiments, the position can be monitored by visually observing the component 230 during delivery to the blood vessel. Alternatively, data related to the current position of the component 230 in the blood vessel (e.g., the monitored position) can be sent to a processor, for example, via a signal emitted by a transmitter incorporated into or otherwise coupled to the neuromodulation catheter. The user can receive feedback signals via a user interface and / or another signal emitting device configured to emit visual, audio, and / or tactile signals according to embodiments of the present technology. In certain embodiments, the position of the neuromodulation component can be monitored in real time.

[0039] In further embodiments, after receiving the catheter position data, the processor can provide a recommendation to the user regarding whether to proceed with the neuromodulation therapy based on whether the current position of the component 230 includes the identified avoidance areas and / or target areas. The recommendation can include a recommendation that the user avoid delivering the neuromodulation therapy to one or more identified areas (e.g., avoidance areas) of the patient's blood vessels or a recommendation that the user deliver the neuromodulation therapy to one or more identified areas (e.g., target areas). In some embodiments, the recommendation can be provided while the neuromodulation catheter is being delivered and / or positioned. In other embodiments, the recommendation can be provided before or after the catheter is being delivered and / or positioned.

[0040] In some embodiments, the recommendation can be provided to the user via a user interface, for example, by displaying the recommendation on a display or emitting a signal. The signal can be a visual signal, an audio signal, a tactile signal, or a combination thereof. For example, a visual signal can be emitted by a device (e.g., a light) that is turned on when component 230 is positioned near one or more identified areas. For example, the recommendation can be a light that turns green when component 230 is positioned near or within an identified target area and / or a light that turns red when positioned near or within an identified avoidance area. In other embodiments, the device can be a speaker, a vibration mechanism, or other device suitable for transmitting a signal to the user. In addition to displaying and / or signaling, the recommendation can be provided to the user by displaying one or more of the hemodynamic parameters and / or overall hemodynamic parameters on a visual display or other device configured to receive hemodynamic parameter(s) and provide the recommendation. In further embodiments, the three-dimensional representation, CFD model, and / or other representation can be stored to guide the positioning of the neuromodulation catheter at a later time, and / or calculations performed after obtaining and / or generating the image and / or representation. In these embodiments, storage, analysis, and / or calculation of images and / or representations may be performed using components of the device and / or environment. Additionally, the processor may provide a report of the distributed hemodynamic parameters to the user on a smartphone, computer, tablet, and / or other device including a digital display.

[0041] Methods of the present technology can include applying neuromodulation energy to at least one of the target areas using a neuromodulation catheter 210. In other embodiments, the target area(s) can be marked as locations for future neuromodulation treatment. When one or more of the hemodynamic parameter(s) rises above a corresponding threshold hemodynamic parameter(s) at a location, the location can be identified as a keep-out area. If neuromodulation energy were to be delivered at the identified keep-out area, there is concern that the patient may have sequelae associated with delivering neuromodulation at that location, such as swelling, edema, stenosis, tearing, rupture, dilation, dissection, and / or thrombosis.

[0042] In further embodiments, the methods and systems described herein can be used to monitor a blood vessel following neuromodulation therapy to determine whether an undesirable event has occurred or is likely to occur. Changes in blood flow and / or blood pressure following neuromodulation therapy can indicate that an undesirable event may have occurred at one or more regions within the region or at another region of the blood vessel. If an undesirable event has indeed occurred, the user can then choose to treat the patient accordingly.

[0043] II. Selected Embodiments of Neuromodulation Systems

[0044] Figure 2 is a partial schematic diagram of a neuromodulation system 200 ("system 200") according to an embodiment of the present technology. System 200 can be used with reference to Figure 1 The method 100 described is used in conjunction with assessing one or more hemodynamic parameters and / or identifying one or more avoidance zones and / or target zones for delivering neuromodulation therapy. Additionally, the system 200 and embodiments thereof can be used to deliver neuromodulation therapy to a patient.

[0045] like Figure 2 As shown in FIG, system 200 includes a neuromodulation catheter 210, a console 295, and a cable 275 operably coupling the neuromodulation catheter 210 to the console 295. The neuromodulation catheter 210 includes an elongated shaft 220 having a proximal portion 220a and a distal portion 220b, a handle 270 operably connected to the shaft 220 at the proximal portion 220a, and a neuromodulation assembly 230 at the distal portion 220b of the shaft 220. The distal portion 220b of the shaft 220 is configured to move within a cavity of a patient and position the neuromodulation assembly 230 at a target area within the cavity. For example, the shaft 220 can be configured to position the neuromodulation assembly 230 within a blood vessel, a duct, an airway, or another naturally occurring cavity within the human body.

[0046] The shaft 220 and the neuromodulation assembly 230 can be 2, 3, 4, 5, 7, or 8 French in size or another suitable size. The dimensions (e.g., outer diameter and length) of the distal portion 220b of the shaft 220 can be selected to accommodate the blood vessel or other body cavity into which the distal portion 220b of the neuromodulation catheter 210 is designed to be delivered. For example, the axial length of the distal portion 220b can be selected to be no longer than the patient's renal artery (e.g., typically less than 8 cm) and to have an expanded or expanded diameter that accommodates the inner diameter of a typical renal artery (e.g., for a renal artery RA, about 2-10 mm, e.g., about 4-8 mm, etc.) and / or branches of the renal artery. Additionally, the neuromodulation assembly 230 can include a shape memory portion having a shape memory material (e.g., nickel titanium alloy) that imparts a helical or spiral shape to the neuromodulation assembly 230 when expanded. In other embodiments, the shaped portion of the neuromodulation assembly 230 may have other dimensions depending on the body lumen in which the shaped portion of the neuromodulation assembly 230 is configured to be deployed.

[0047] As shown, the neuromodulation assembly 230 includes a sensor 240, a transmitter 245, and a plurality of energy delivery elements 260a-g (collectively, energy delivery elements 260). In this embodiment, the sensor 240 is disposed at the distal end (e.g., the distal tip) of the distal portion 220b, and the transmitter 245 is disposed proximal to the energy delivery elements 260. In other embodiments, the sensor 240 and / or the transmitter 245 can be disposed at different locations suitable for the sensor 240 to detect one or more hemodynamic parameters and / or for the transmitter 245 to transmit the position of the neuromodulation assembly 230 to the receiver 287 according to the embodiments described herein. For example, the sensor 240 can be proximal to one or more energy delivery elements 260 and / or the transmitter 245 can be distal to one or more energy delivery elements 260. The sensor 240 and the transmitter 245 can be connected to one or more power supply lines (not shown) that transmit energy to the sensor 240 and the transmitter 245. Alternatively, the sensor 240 and / or transmitter 245 can be operably coupled to the console 295 via a dedicated line and / or wirelessly (e.g., Bluetooth, radio waves, etc.). In embodiments where the sensor 240 or transmitter 245 is not located at the distal end of the catheter, the neuromodulation assembly 230 can have an atraumatic tip (not shown). In certain embodiments, the neuromodulation assembly 230 can include more than one sensor 240 and / or transmitter 245. The sensor 240, transmitter 245, and neuromodulation assembly 230 can be integrated into a single neuromodulation catheter 210 as shown, or one or more of the sensor 240 and / or transmitter 245 can be provided separately from the neuromodulation catheter 210, as will be discussed below.

[0048] Sensor 240 can detect physiological parameters (such as hemodynamic parameters), and transmitter 245 can transmit a signal related to the position of neuromodulation assembly 230 in the blood vessel to receiver 287. Sensor 240 may include one or more sensors, such as a blood velocity sensor (e.g., a Doppler laser velocity sensor or an ultrasonic flowmeter) that can detect blood flow through a blood vessel (e.g., a renal artery RA), a pressure sensor that measures blood pressure within the blood vessel, a blood impedance sensor (e.g., a single-electrode or multi-electrode) that can determine changes in blood vessel diameter, and / or other suitable sensors for detecting one or more hemodynamic parameters. As will be understood by those skilled in the art, blood is more conductive than vascular tissue, and thus, blood vessel impedance (i.e., blood impedance) is lower when the blood vessel has a larger diameter (i.e., when the vessel contains more blood) and higher when the blood vessel has a smaller diameter (i.e., when the vessel contains less blood). Therefore, when sensor 240 is a single-electrode or multi-electrode impedance sensor, the blood impedance measurement acquired by sensor 240 can be correlated with changes in blood vessel diameter, segment volume, and / or cross-sectional area (i.e., hemodynamic response). In some embodiments, the blood impedance measurement can be used to assess the efficacy of neuromodulation therapy. Similar to vessel diameter, blood flow and blood pressure are expected to change in response to stimulation, and these changes are expected to occur to a lesser extent after neuromodulation than before neuromodulation. Thus, changes in blood flow and / or vascular pressure measurements caused by electrical or pharmacological stimulation can be detected before and after neuromodulation and then compared to thresholds to determine the efficacy of the neuromodulation treatment. Further embodiments of monitoring hemodynamic responses to stimulation are disclosed in PCT patent application No. PCT / US15 / 534999, entitled “Systems and Methods for Evaluating Neuromodulation Therapy via Hemodynamic Responses,” filed on October 1, 2015, which is incorporated herein by reference in its entirety.

[0049] In some embodiments, sensor 240 can detect more than one hemodynamic parameter in a blood vessel. For example, sensor 240 may include sensors configured to detect blood flow and blood pressure in a renal artery. In other embodiments, sensor 240 may include different or additional sensors that detect and / or record other information, such as one or more of temperature (e.g., thermocouples, thermistors, etc.), optical, chemical, and / or other parameters. Sensor 240 sensor(s) may be further configured to record data associated with the detected hemodynamic parameters. In some embodiments, the recording may be performed by another component of system 200.

[0050] Transmitter 245 may include one or more sensors configured to monitor the position of neuromodulation assembly 230 within a blood vessel, e.g., a first sensor, a second sensor, a third sensor, a fourth sensor, etc. In some embodiments, each sensor of transmitter 245 may be configured to monitor the position of a specific energy delivery element 260 (e.g., an electrode). For example, the first sensor may be configured to monitor the position of energy delivery elements 260a and 260b, the second sensor may be configured to monitor the position of energy delivery elements 260c and 260d, the third sensor may be configured to monitor the position of energy delivery elements 260e and 260f, and the fourth sensor may be configured to monitor the position of energy delivery element 260g. In other embodiments, each sensor may have a specific range and may monitor the position of any portion of neuromodulation assembly 230, or the position of the transmitter relative to any feature of the blood vessel (e.g., a wall, an ostium, a bifurcation, etc.) within the range. The sensor(s) of transmitter 245 may be further configured to record data associated with the monitored position. In some embodiments, the position recording may be performed by another component of system 200.

[0051] In other embodiments, the neuromodulation assembly 230 may have fewer or more than seven energy delivery elements 260. Figure 2As shown in FIG, the neuromodulation assembly 230 includes seven energy delivery elements 260a-g. The energy delivery elements 260 can be configured to apply electrical stimulation (e.g., RF energy) to an identified target area at or near one or more blood vessels in the patient's body to temporarily paralyze (stun) nerves, and / or deliver neuromodulation energy to the target area. The energy delivery elements 260 can be connected to one or more power supply lines (not shown) that transmit energy to the energy delivery elements 260. In some embodiments, the energy delivery elements 260 are electrodes. In various embodiments, certain energy delivery elements 260 can be dedicated to applying stimulation, and other energy delivery elements 260 can be other types of therapeutic elements (such as transducers or other elements) to deliver energy to modulate perivascular nerves using other suitable neuromodulation modalities (such as pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intravascularly delivered ultrasound, extracorporeal ultrasound, and / or high-intensity focused ultrasound (FIFU)), direct thermal energy, radiation (e.g., infrared, visible light, and / or gamma radiation), and / or other suitable types of energy). In certain embodiments, the neuromodulation catheter 210 can be configured for cryotherapy, and cryogenic cooling can be applied to the renal artery RA using a refrigerant (e.g., via a balloon catheter that circulates the refrigerant). In this embodiment, the system 200 may include a refrigerant reservoir (not shown) coupled to the neuromodulation catheter 210 and may be configured to supply refrigerant to the neuromodulation catheter 210. In yet other embodiments, the neuromodulation catheter 210 is configured for chemical-based therapy (e.g., drug infusion), and the neuromodulation catheter 210 may distribute one or more chemicals to the treatment area intraluminally or inject one or more chemicals into the treatment area transluminally to achieve neuromodulation. These chemicals may include neurotoxins (e.g., ethanol), adrenergic antagonists (e.g., guanethidine), and / or tissue necrosis inducers (e.g., ethanol). In this embodiment, the system 200 may include a chemical reservoir (not shown) and may be configured to supply one or more chemicals to the neuromodulation catheter 210. In certain embodiments, one or more sensors and / or transducers may be located near, within, or integral to the energy delivery element 260 .

[0052] Energy delivery elements 260 (e.g., electrodes) can be positioned on the neuromodulation assembly 230 in a variety of patterns in one or more planes. In the embodiment shown, the energy delivery elements 260 are positioned on the shape memory portion of the neuromodulation assembly 230 so that many or all of the energy delivery elements 260 are pressed against or otherwise contact the internal vessel wall (e.g., the renal artery RA wall). In other embodiments, multiple energy delivery elements 260 can be positioned in the same plane orthogonal to the renal artery RA to deliver stimulation and / or obtain multiple recordings in the same plane of the internal vessel wall. When in contact with the internal vessel wall, the energy delivery element 260 and / or another type of energy delivery element can deliver neuromodulation energy to the target area to modulate or ablate nerves near the target area. A successful or effective neuromodulation treatment or therapy (i.e., when the nerves are ablated to the desired extent) is expected to stop or reduce neural activity.

[0053] Although the illustrated embodiment of the neuromodulation assembly 230 is configured with a helical / spiral shape, in other embodiments, the distal portion 220b of the shaft 220 can have other suitable shapes (e.g., semicircular, curved, straight, etc.), and / or the neuromodulation catheter 210 can include a plurality of support members configured to carry and press one or more energy delivery elements 260 against the interior vessel wall. Other suitable devices and techniques are described, for example, in the following applications: U.S. Patent Application No. 12 / 910,631, filed October 22, 2010; U.S. Patent Application No. 13 / 279,205, filed October 21, 2011; U.S. Patent Application No. 13 / 279,330, filed October 23, 2011; U.S. Patent Application No. 13 / 281,360, filed October 25, 2011; U.S. Patent Application No. 13 / 281,360, filed October 25, 2011; and U.S. Patent Application No. 13 / 281,360, filed October 25, 2011. / 281,361; PCT Application No. PCT / US11 / 57754, filed October 25, 2011; U.S. Provisional Patent Application No. 71 / 646,218, filed May 5, 2012; U.S. Patent Application No. 13 / 793,647, filed March 11, 2013; U.S. Provisional Patent Application No. 71 / 961,874, filed October 24, 2013; and U.S. Patent Application No. 13 / 670,452, filed November 7, 2012. All of the above applications are incorporated herein by reference in their entirety. Non-limiting examples of devices and systems include Symplicity TM RF ablation catheters and Symplicity Spyral TM Multi-electrode RF ablation catheter.

[0054] The console 295 of the system 200 may be configured to control, monitor, supply, and / or otherwise support the operation and function of the neuromodulation catheter 210. Figure 1 CFD modeling. Figure 2 As shown, console 295 includes controller 280, processor 285, receiver 287, and user interface 297. For example, the CFD model generated by method 100 and its embodiments can be displayed as one or more images 298 on user interface 297. In other embodiments, the user interface can be a separate component (such as a monitor (not shown)) that displays image 298, rather than having user interface 297 integrated with console 295. In some embodiments, console 295 can have more than one user interface 297, or system 200 can have a separate monitor (not shown) and user interface 297 integrated with console 295. Console 295 can be configured to generate a selected form of energy and / or a selected amplitude of energy for delivery to tissue at a target area via neuromodulation assembly 230, and thus, console 295 can have different configurations depending on the treatment modality of neuromodulation catheter 210. For example, when the neuromodulation catheter 210 is configured for electrode-based therapy, thermal element-based therapy, or transducer-based therapy, the console 295 may include an energy generator (not shown) configured to generate RF energy (e.g., monopolar and / or bipolar RF energy), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intravascularly delivered ultrasound, extracorporeal ultrasound, and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible light, and / or gamma radiation), and / or another suitable type of energy.

[0055] In selected embodiments, the console 295 and the neuromodulation catheter 210 can be configured to deliver a monopolar electric field via one or more of the energy delivery elements 260. In such embodiments, a neutral or dispersive energy delivery element (not shown) can be electrically connected to the console 295 and attached to the exterior of the patient. In embodiments comprising multiple energy delivery elements 260, the energy delivery elements 260 can deliver power independently, simultaneously, selectively, or sequentially in a monopolar manner, and / or can deliver power between any desired combination of energy delivery elements 260 in a bipolar manner. Additionally, a user can manually select which energy delivery elements 260 are activated for power delivery in order to form highly customized lesion(s) within a cavity (e.g., a renal artery) as desired.

[0056] The controller 280 and the processor 285 may define a computing device that includes memory and is configured to receive and store imaging data, hemodynamic data (e.g., measured values ​​of hemodynamic parameters detected by the sensor 240), and / or position data (e.g., magnetic signals transmitted by the transmitter 245). The memory may be configured to store instructions that, when executed by the computing device, cause the system 200 to perform certain operations according to the present technology, such as performing the operations described above with reference to FIG. Figure 1 Embodiments of blocks 110 , 120 , 130 , 140 , and 150 of method 100 are described.

[0057] In addition to avoiding delivery of neuromodulation energy at one or more avoidance zones as described above, additional embodiments of methods and systems of the present technology can determine efficacy and / or risk to optimize the neuromodulation process. For example, sensor 240 can be positioned proximal to the treatment area to detect or measure one or more hemodynamic parameters after application of neuromodulation energy. Additionally, transmitter 245 can be positioned near the treatment area (e.g., proximal or distal) to transmit information to the user regarding the position of neuromodulation assembly 230 within the blood vessel. Controller 280 can include an algorithm that generates a comparison of pre-neuromodulation and post-neuromodulation information (e.g., hemodynamic parameters, imaging data, etc.) about the patient. Because one or more hemodynamic parameters can change in response to energy delivery, this comparison can provide the user with an indication of whether the neuromodulation treatment is effective and / or whether an actual undesirable event or risk of an actual undesirable event exists. In certain embodiments, this comparison can reference standardized or patient-specific threshold changes or levels that indicate therapeutically effective neuromodulation and / or the risk of an undesirable event. This comparison can be provided to the user via user interface 297 or other components (e.g., a monitor). Based on this comparison, the user can determine whether the neuromodulation treatment has achieved the desired effect, or whether the treatment has affected hemodynamic parameters and / or structural characteristics of the blood vessel (e.g., wall thickness, rupture, intimal delamination, etc.). If the comparison indicates that the neuromodulation treatment is ineffective and / or the risk of experiencing an undesirable event has increased, subsequent monitoring and / or subsequent treatment procedures can be performed. For example, the neuromodulation assembly 230 can be repositioned and / or rotated along the blood vessel (e.g., the renal artery RA) to modulate nerves at different locations or in different planes.

[0058] Figure 3 According to another embodiment of the present technology Figure 22 is a side view of a neuromodulation assembly 230 positioned within a renal blood vessel. In other embodiments, the neuromodulation catheter 210 can be positioned in other blood vessels for delivering neuromodulation therapy at different regions within a human patient. As shown, the system 200 includes a guide catheter 320 configured to intravascularly position a distal portion 220b of the neuromodulation catheter 210 at a treatment region within a blood vessel (e.g., a renal artery RA). In operation, intraluminal delivery of the neuromodulation assembly 230 can include percutaneously inserting a guidewire (not shown) into a body cavity of the patient and moving the shaft 220 ( Figure 2 ) and / or the neuromodulation assembly 230 until the neuromodulation assembly 230 reaches the target area (e.g., the renal artery). For example, the distal end of the neuromodulation assembly 230 can define a channel for engaging a guidewire for delivering the neuromodulation assembly 230 using over-the-wire (OTW) or rapid exchange (RX) technology. In other embodiments, the neuromodulation catheter 210 can be a steerable or non-steerable device that is configured to be used without a guidewire. In yet other embodiments, the neuromodulation catheter 210 can be configured for delivery via a sheath (not shown).

[0059] During the procedure, the neuromodulation assembly 230 extends distally of the distal portion 330 of the guide catheter 320 and enters the vessel lumen. For example, as the neuromodulation assembly 230 advances through the vessel lumen, the sensor 240 senses laminar blood flow through the proximal portion of the lumen. When the neuromodulation assembly encounters a potential avoidance area, such as a stenosis 351 and / or a bifurcation 315, the sensor 240 detects a change in the previous laminar blood flow. The sensor 240 transmits the blood flow data to the receiver 287, and as described above, other components of the system 200 generate a CFD model based in part on the blood flow data. As described above, the system 200 identifies and recommends avoidance areas and target areas for delivering neuromodulation energy.

[0060] Once positioned in the target vessel, the neuromodulation assembly 230 transitions from a low-profile delivery state (not shown) for delivery (e.g., intravascularly through the aorta) to an expanded state (e.g., a radially expanded state). When deployed, the energy delivery element 260 presses against the inner wall of the vessel, and neuromodulation energy can be selectively delivered to the identified target area. After delivering the neuromodulation energy, the system 200 is configured to sense post-neuromodulation treatment parameters and determine efficacy and / or risk of undesirable events, as described above. If desired, the user can reposition the neuromodulation assembly 230 to deliver additional neuromodulation therapy at one or more different identified target locations. To reposition the neuromodulation assembly 230, the user can return the assembly 230 to the low-profile delivery state and redeploy the neuromodulation assembly 230 at the new location. In some embodiments, the position of the neuromodulation assembly 230 during positioning, deployment, repositioning, redeployment, and / or a combination thereof can be displayed in real time on the user interface 297.

[0061] Figure 4 A representation of a blood vessel according to an embodiment of the present technology ("representation 400") is shown. Representation 400 is a CFD image 407 that displays visual indicators corresponding to a target region 440, a potential region 450, and an avoidance region 460 determined according to an embodiment of blocks 110, 120, 130, and 140 of method 100. CFD image 407 depicts blood vessel 405, which includes a proximal portion 430a and a distal portion 430b, with a primary portion of blood vessel 405 extending between proximal portion 430a and distal portion 430b. CFD image 407 further depicts a right branch 410 and a left branch 420 extending from blood vessel 405 at bifurcation 415 into right portion 430d and left portion 430c, respectively. In the illustrated embodiment, avoidance region 460 is indicated by dense hashing, target region 440 is indicated by sparse hashing, and potential region 450 is shown by medium hashing. In other embodiments, avoidance zone 46, potential zone 450, and target zone 440 may be individually indicated by color, shades of color, more than one color, shades of more than one color, one or more patterns, shapes, and / or combinations thereof. For example, avoidance zone 460 may be indicated by a red marker, potential zone 450 by a yellow marker, and target zone 440 by a green marker, where each marker encloses the boundaries of a corresponding zone.

[0062] In some embodiments, neuromodulation component 230 (not shown) can be positioned in blood vessel 405 while the user is viewing representation 400. Figure 2 and Figure 3For example, the representation 400 can guide the positioning of the neuromodulation assembly 230 within a blood vessel, where the user can visually determine where the neuromodulation assembly 230 is located relative to the avoidance zone 460, the potential zone, or the target zone 440. Thus, the clinician can refer to the representation 400 and select or deselect particular energy delivery elements 260 to avoid delivering neuromodulation therapy to the patient at the identified and displayed avoidance zone 460 and instead deliver therapy to the identified and displayed target zone 440.

[0063] In some embodiments, an auditory signal, a tactile signal, or a combination thereof can be combined with representation 400 to alert the user of the location of neuromodulation assembly 230. For example, an auditory signal and / or a tactile signal can alert the user when one or more energy delivery elements 260 of neuromodulation assembly 230 are located within an identified avoidance zone 460, or alternatively, within an identified target zone 440. Alternatively, the auditory signal and / or the tactile signal can include multiple signals, where each signal (e.g., a tone, a vibration, a repetition of a signal, etc.) corresponds to a specific energy delivery element 260 located within a specific zone. Using a multi-electrode catheter such as catheter 210, a clinician can operate console 295 to individually test each energy delivery element 260 to obtain a signal indicating the potential risks or benefits of administering neuromodulation energy at each element's current location. For example, a first signal can correspond to an energy delivery element 260 located within avoidance zone 460, a second signal can correspond to a second energy delivery element 260 located within potential zone 450, and a third signal can correspond to a third energy delivery element 260 located within target zone 440. Similar to the displayed indicator, an auditory signal and / or a tactile signal can be transmitted to the user in real time when neuromodulation assembly 230 is positioned, regardless of whether the position of neuromodulation assembly 230 is visible in real time on representation 400. In some embodiments, only a visual indicator is displayed on representation 400, only an auditory signal is transmitted to the user, or only a tactile signal is transmitted to the user.

[0064] Figure 5is a partial schematic diagram of a neuromodulation system 500 ("system 500") configured in accordance with another embodiment of the present technology. Certain features of system 500 are generally similar to other embodiments of the present technology described herein. System 500 differs from system 200 in that the transmitter 245 is carried by a separate catheter or guidewire 555. In the illustrated embodiment, the sensor 240 is located at the distal-most end (e.g., the tip) of the distal portion 220b, and the transmitter 245 is positioned along the length of the guidewire 555. In other embodiments, the sensor 240 can be at other locations along the length of the distal portion 220b (e.g., on the neuromodulation assembly 230) and / or the transmitter 245 can be at the distal-most end (e.g., the tip) of the guidewire 555. The shaft 220 and the guidewire 555 can be integrated into a single neuromodulation catheter 210, or, alternatively, they can be in separate components.

[0065] In other embodiments, the transmitter 245, rather than the sensor, may be located at the distal portion 220b of the shaft 220, and the sensor 240 may be carried by the guidewire 555. In embodiments where the neuromodulation catheter 210 includes more than one sensor 240 and / or more than one transmitter 245, some of the sensors and / or some of the transmitters may be carried by the distal portion 220b of the shaft 220 and other of the sensors and / or other of the transmitters may be carried by the guidewire 555. In other embodiments, the sensor 240 may be mounted on a portion of a guide catheter that is insertable into a blood vessel receiving neuromodulation therapy.

[0066] Figure 6 According to an embodiment of the present technology Figure 5 FIG2 is a side view of a distal portion of a neuromodulation assembly 230 and a guidewire 555 positioned within a blood vessel. As described above, the sensor 240 can be coupled to one of the shaft 220 or the guidewire 555, while the transmitter 245 is coupled to the other. In this way, the sensor 240 and the transmitter 245 can be delivered independently of each other.

[0067] In the illustrated embodiment, the sensor 240 is coupled to the shaft 220 and delivered along with the neuromodulation assembly 230 to a first location along a blood vessel (e.g., the renal artery RA) via the guide catheter 320. Once the catheter 210 is positioned, a guidewire 555 having a transmitter 245 is delivered to a second location proximate to the first location via the guide catheter 320. For clarity, Figure 6The neuromodulation assembly 230 is shown not fully deployed within the vessel, and the guidewire 555 is positioned alongside the assembly 230. It is contemplated that in a typical deployment, the neuromodulation assembly 230 is fully deployed within the vessel, such that each energy delivery element 260 contacts the vessel wall as closely as possible, and the guidewire 555 is positioned within the assembly 230. The user can activate the sensor 240 to detect one or more hemodynamic parameters at a first location, and can activate the transmitter 245 to transmit the location of the neuromodulation assembly 230 to the receiver 287. As described above with reference to Figure 2 and Figure 3 As described, the system 500 identifies whether each energy delivery element 260 is located at an identified target area or an identified avoidance area. If the energy delivery element 260 is positioned at an identified target area as shown on the user interface 297, the user can deliver neuromodulation therapy through the element. If the energy delivery element 260 is positioned near an identified avoidance area (e.g., near a stenosis 351, a sinus ostium 310, or a bifurcation 315), the user can skip delivering neuromodulation therapy through the element, and / or reposition the neuromodulation assembly 230 and the guidewire 555 to identify one or more target areas in the blood vessel. Alternatively, the user can reposition the transmitter 245 adjacent to each of the energy delivery elements 260a-g to determine whether the energy delivery element 260 is near the identified target area.

[0068] like Figure 6 , sensor 240 is located distal to energy delivery element 260g and emitter 245 is positioned substantially adjacent to energy delivery element 260f in the blood vessel. In other embodiments, sensor 240 can be located proximal to at least one energy delivery element 260 and emitter 245 can be positioned substantially adjacent to, substantially proximal to, or distal to another energy delivery element 260. In further embodiments, guidewire 555 can be delivered to a first location in a blood vessel (e.g., a renal artery RA) prior to neuromodulation assembly 230. For example, if a CFD model of the patient's blood vessel is generated before emitter 245 is delivered (such as during a previous procedure or as part of a previous positioning), the user may have previously identified a desired target location to deliver neuromodulation therapy. In this embodiment, the user can activate emitter 245 to locate the desired target location and position the energy delivery element of neuromodulation assembly 230 at the desired location.

[0069] Figure 7-9 The diagram is an anatomical and conceptual side, cross-sectional, and exploded view of a blood vessel illustrating various physiological and pathological features. Although the configuration of a blood vessel can have many variations and / or a blood vessel can have localized flow abnormalities, Figure 7-9The figures are shown for illustrative purposes and are not intended to exaggerate or limit the number, location, configuration, and / or localized flow anomalies that may occur in a blood vessel. As described above, delivering perivascular neuromodulation therapy to identified avoidance areas (e.g., specific locations having one or more physiological characteristics, pathological characteristics, and / or blood flow anomalies) may result in undesirable events. Therefore, the method 100, system 200, 500, and embodiments thereof can help clinicians avoid such undesirable areas while also guiding the user to the desired target area.

[0070] like Figure 7 As shown in FIG, a main vessel 705 branches into two branches at a bifurcation 315, including a right branch 712 and a left branch 716. At the bifurcation 315, the branched vessels form a carina in the vessel wall (shown in a detailed view). A lumen 710 extends through the main vessel 705 and separates into a right lumen 714 and a left lumen 718 in each branch. Blood can flow through the lumen 710 and can be divided into a right stream 733 and a left stream 732 at the bifurcation 315. Through a linear (e.g., straight) portion of a vessel with a healthy lumen (e.g., smooth walls and a normal inner diameter to allow blood to flow without interference), blood flow is generally laminar and imposes physiological shear stress (e.g., hemodynamic stress) on the vessel wall. This wall shear stress (WSS) can be measured as the force per unit area exerted on the vessel wall and can be affected by blood viscosity and blood flow. Physiological (e.g., healthy) WSS in the venous system is about 1 to about 7 dyne / cm 2 , about 10 to about 15 dyne / cm in the arterial system 2 The flow into the right branch 712 and the left branch 716 exerts about 27 dynes / cm on the vessel wall at the bifurcation 315. 2 or greater. For example, sudden geometric changes in the vessel wall, such as bifurcations 315, are subject to HWSS. In addition, when the flow trajectory changes and the blood contacts the vessel wall in a non-laminar manner, the blood flow can become turbulent and / or form vortices 735, such as Figure 7 For example, the vortex 735 can reduce the normal wall shear stress to a relatively low wall shear stress (LWSS), such as about 12.6 dynes / cm 2 or lower. These regions of LWSS often occur distal to abrupt geometric changes (e.g., bifurcation 315) and / or in areas adjacent to HWSS. Additionally, the wall shear stress at a location in a vessel can vary, for example, having both HWSS and LWSS at a portion of the vessel (i.e., at bifurcation 315 or at tapered region 760).

[0071] In addition to the aforementioned physiological changes in vessel geometry, blood flow can also be altered by pathological events, such as changes in the vessel wall. For example, thickened portions of the vessel wall, such as at stenosis 351, impede laminar flow 754 in region 750. As shown, the left lumen 718 narrows at stenosis 351, causing laminar flow 754 to become turbulent 756 along the distal portion of the region of impinging flow 750. Vascular calcification 720 occurs through the formation and / or deposition of calcium 727 in the vessel wall. While calcium deposits can be located in the intima 721 and / or adventitia 723, deposits are most commonly found in the tunica media 725. A portion of the vessel wall with calcification 720 (e.g., calcium deposits) is less elastic and has an impaired ability to respond to changes in blood flow, blood pressure, etc., compared to non-calcified areas.

[0072] like Figure 8 and Figure 9 As shown in , the vessel wall has other diseases that can cause undesirable events in response to the delivery of neuromodulation therapy. For example, Figure 8 A main vessel 810 is shown that branches into a left branch 820 and a right branch 825 having fibromuscular dysplasia in an area 830. A lumen 840 extends from the main vessel 810 into the left branch 820 and through the area 830 having fibromuscular dysplasia. Referring to the enlarged cross-sectional view 860, fibromuscular dysplasia results in an abnormal thickening of the vessel wall 850. While not intended to be limiting, Figure 8 The multifocal type of fibromuscular dysplasia is shown as distinguished from the focal and adventitial types. Fibromuscular dysplasia can affect many different blood vessels; however, the most common vessels include the carotid arteries, vertebral arteries, renal arteries, and arteries that couple to the arms, legs, and intestines.

[0073] The blood vessel wall can also be altered by the formation of an aneurysm, which is a localized dilation or bulge in the blood vessel wall that may be associated with high blood pressure and / or may occur at a weakened portion of the blood vessel wall. Aneurysms are generally classified by their location (e.g., artery, vein, heart, coronary artery, aorta, brain, leg, kidney, and capillary). Figure 9 As shown in FIG, a main vessel 905 has a lumen 910 extending from a proximal portion 905a through a distal portion 905b. An aneurysm 920 is located between the proximal portion 905a and the distal portion 905b. Referring to the enlarged cross-sectional view 925, the aneurysm 920 includes a large lumen 930 (e.g., extending from the lumen 910), an outer wall 940a, and an inner wall 940b. Although not intended to be limiting, Figure 9 Shown is a saccular aneurysm 920, which is one of several types of aneurysms including fusiform and microaneurysms.

[0074] Figure 10 (See also Figure 2-6 ) shows modulation of renal nerves using a neuromodulation catheter as described herein according to an additional embodiment of the present technology. Neuromodulation catheter 210 provides access to the renal plexus RP through an intravascular pathway P, such as a percutaneous access area in the femoral artery (shown), brachial artery, radial artery, or axillary artery, to a target treatment area within a corresponding renal artery RA. By manipulating the proximal portion 220a of the shaft 220 from outside the intravascular pathway P, the clinician can advance the shaft 220 through the sometimes tortuous intravascular pathway P and remotely manipulate the distal portion 220b of the shaft 220 ( Figure 2-6 ).exist Figure 10 In the illustrated embodiment, the neuromodulation assembly 230 is delivered intravascularly to the treatment area using the OTW technique using the guidewire 1010. At the treatment area, the guidewire 1010 can be at least partially withdrawn or removed, and the neuromodulation assembly 230 can be transformed or otherwise moved to an expanded arrangement for delivering energy at the treatment area. In other embodiments, the neuromodulation assembly 230 can be delivered to the treatment area within a guide sheath (not shown) with or without the use of the guidewire 1010. When the neuromodulation assembly 230 is at the target area, the guide sheath (if used) can be at least partially withdrawn or retracted so that the neuromodulation assembly 230 can be transformed into an expanded configuration. In yet other embodiments, the shaft 220 itself can be maneuverable so that the neuromodulation assembly 230 can be delivered to the treatment area without the aid of the guidewire 1010 and / or the guide sheath.

[0075] In addition to the methods 100, systems 200, 500, and embodiments thereof described herein with respect to assessing hemodynamics for optimizing delivery of neuromodulation therapy, image guidance (e.g., computed tomography (CT), fluoroscopy, intravascular ultrasound (IVUS), optical coherence tomography (OCT), intracardiac echocardiography (ICE), or another suitable guidance modality, or a combination thereof) may also assist a clinician in positioning and maneuvering the neuromodulation catheter 210 in accordance with the present technology. For example, a fluoroscopy system (e.g., including a flat panel detector, x-ray, or C-arm) may be rotated to accurately visualize and identify a target treatment area. In other embodiments, the treatment area may be determined prior to delivery of the neuromodulation catheter 230 using IVUS, OCT, and / or other suitable image mapping modalities that may correlate the target treatment area with an identifiable anatomical structure (e.g., a spinal feature) and / or a radiopaque ruler (e.g., positioned beneath or above the patient). Further, in some embodiments, an image guidance component (e.g., IVUS, OCT) can be integrated with the neuromodulation catheter 210 and / or run in parallel with the neuromodulation catheter 210 to provide image guidance during positioning of the neuromodulation assembly 230. For example, an image guidance component (e.g., IVUS or OCT) can be coupled to the neuromodulation assembly 230 to provide a three-dimensional image of the vasculature proximate to the target area to facilitate positioning or deploying the neuromodulation assembly 230 within the target vessel. As described above, the method 100, system 200, 500, and embodiments thereof may include determining the location of avoidance areas and / or target areas for delivering neuromodulation therapy and transmitting the location information to a user. The image guidance modalities described herein can be used in conjunction with the methods, systems, and embodiments of the present technology to provide the user with location information of the neuromodulation catheter 210 in real time.

[0076] The light from electrode 260 ( Figure 2-6) and / or other energy delivery elements are applied to the identified target tissue to induce one or more desired neuromodulatory effects on a localized region of the renal artery RA and an adjacent perivascular region of the renal plexus RP, which is located closely within, adjacent to, or in close proximity to the adventitia of the renal artery RA. The targeted application of energy can achieve neuromodulation along all or at least a portion of the renal plexus RP. The neuromodulatory effect is generally at least in part a function of power, time, contact between the energy delivery element and the vessel wall, and blood flow through the vessel. The neuromodulatory effect can include denervation, thermal ablation, and / or non-ablative thermal change or injury (e.g., via continuous heating and / or resistive heating). The desired thermal heating effect can include raising the temperature of the target nerve fibers above a desired threshold to achieve non-ablative thermal change, or above a higher temperature to achieve ablative thermal change. For example, the target temperature can be above body temperature (e.g., approximately 37° C.) but less than approximately 45° C. for non-ablative thermal change, or the target temperature can be approximately 45° C. or higher for ablative thermal change. Desirable non-thermal neuromodulatory effects may include altering electrical signals transmitted in nerves.

[0077] The cryogenic effect can also provide neuromodulation. For example, a cryotherapy applicator can be used to cool tissue at a target area to provide therapeutically effective direct cell damage (e.g., necrosis), vascular damage (e.g., by destroying the supplying blood vessels so that the cells die from lack of nutrients) and sublethal hypothermia with subsequent apoptosis. Exposure to cryogenic cooling may result in acute cell death (e.g., death immediately after exposure) and / or delayed cell death (e.g., death during tissue thawing and subsequent transition perfusion). Several embodiments of the present technology may include cooling a structure that is at or near the inner surface of the renal artery wall so that the adjacent (e.g., adjacent) tissue is effectively cooled to the depth where the renal sympathetic nerves reside. For example, the cooling structure is cooled to such an extent that it causes therapeutically effective low-temperature renal neuromodulation. It is expected that sufficient cooling of at least a portion of the renal sympathetic nerves will slow or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity.

[0078] like Figure 11 As shown, at least a portion of a CFD model can be generated using the systems 200 and 500, the device 1100, and the environment 1200 described below according to the present technology. For example, a CFD workflow can be partially performed by a computer 1110 that is configured to execute instructions (e.g., one or more software applications 1164 and 1166 for facilitating the operation of the CFD workflow) for generating a CFD model. In some embodiments, reference is made to Figure 12, the CFD model may be saved to and / or stored at one or more servers 1220 (eg, a central server).

[0079] Figure 11 is a block diagram illustrating an overview of a device on which some embodiments of the present technology may operate. The device may include hardware components of a device 1100 for analyzing imaging data and hemodynamic parameters of a patient, comparing one or more of the patient's hemodynamic parameters and / or optimized parameters to threshold hemodynamic parameters, and providing a recommendation such as whether to deliver neuromodulation at a location in a blood vessel. For example, the device 1100 may be incorporated into the device referenced above. Figure 2 The console 295 is described.

[0080] Device 1100 may include, for example, one or more input devices 1120 that provide input to a central processing unit ("CPU"; processor) 1110 and notify the CPU 1110 of actions. These actions are typically mediated by a hardware controller that interprets signals received from the input devices and transmits the information to the CPU 1110 using a communication protocol. Input devices 1120 include, for example, for receiving inputs from a monitoring device (e.g., a reference signal). Figure 2-6 The sensors 240 and / or transmitters 245 described herein may include a receiver that receives signals, a mouse, a keyboard, a touch screen, an infrared sensor, a touchpad, a wearable input device, a camera-based or image-based input device, a microphone, and / or other user input devices.

[0081] The CPU 1110 may be a single processing unit in a device or multiple processing units distributed across multiple devices. The CPU 1110 may be coupled to other hardware devices using, for example, a bus such as a PCI bus or a SCSI bus. The CPU 1110 may communicate with hardware controllers for devices such as a display 1130. The display 1130 (which may be a console 295 ( Figure 2) can be used to display text and graphics. In some examples, the display 1130 provides graphical and textual visual information to the user, such as information related to one or more of the patient's hemodynamic parameters (e.g., individual and compared to threshold hemodynamic parameters), a summary of data detected by one or more sensors 240 and / or emitters 245 coupled to the device 1100, and / or other suitable information. In some embodiments, the display 1130 includes an input device as part of the display, such as when the input device is a touch screen or the input device is equipped with an eye direction monitoring system. In some embodiments, the display 1130 is separate from the input device 1120. Examples of display devices are: LCD display screens, LED display screens, projection, holographic, or augmented reality displays (such as head-mounted display devices or head-mounted devices), etc. Other input / output (I / O) devices 1140 may also be coupled to the processor, such as a network card, video card, audio card, USB, FireWire or other external devices, camera, printer, speakers, CD-ROM drive, DVD drive, disk drive, or Blu-ray device.

[0082] In some embodiments, the device 1100 also includes a communication device capable of communicating with a network node wirelessly or by wire. The communication device can communicate with another device or server via a network using, for example, the TCP / IP protocol. The device 1100 can utilize the communication device to distribute operations across multiple network devices.

[0083] The device 1100 may execute the above reference Figure 1100 . To execute these embodiments, the CPU 1110 may be configured to access a memory 1150 . The memory includes one or more of various hardware devices for volatile and non-volatile storage and may include both read-only and writeable memory. For example, the memory 1150 may include random access memory (RAM), CPU registers, read-only memory (ROM), and writeable non-volatile memory such as flash memory, hard drives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives, device buffers, and the like. The memory is not a propagating signal separate from the underlying hardware; therefore, the memory is non-transient. The memory 1150 may include a program memory 1160 for storing programs and software, such as an operating system 1162 , a hemodynamic parameter analysis program 1164 , and other application programs 1166 . For example, the hemodynamic parameter analysis program 1164 may include one or more algorithms for analyzing various indices related to one or more hemodynamic parameters, providing a hemodynamic parameter summary or report, or other information related to delivering neuromodulation therapy to a patient based on the hemodynamic parameters. The memory 1150 may also include a data storage 1170 that includes sensed data and / or recorded data from one or more of the sensors, patient data, algorithms related to hemodynamic parameter analysis, configuration data, settings, user options or preferences, etc., which may be provided to the program storage 1160 or any component of the device 1100.

[0084] Certain embodiments may be operated with numerous other general-purpose or special-purpose computing system environments or configurations. Examples of well-known computing systems, environments, and / or configurations suitable for use with the present technology include, but are not limited to, personal computers, server computers, handheld or laptop devices, cellular phones, wearable electronic devices, tablet devices, multiprocessor systems, microprocessor systems, microprocessor-based systems, set-top boxes, programmable consumer electronic devices, network PCs, minicomputers, mainframe computers, distributed computing environments including any of the above systems or devices, and the like.

[0085] Figure 12 is a block diagram illustrating an overview of an environment 1200 in which some embodiments of the disclosed technology may operate. The environment 1200 may include one or more client computing devices 1205A-D (collectively referred to as "client computing devices 1205"). Examples of client computing devices 1205 may include Figure 11The client computing device 1205 may operate in a networked environment using logical connections through a network 1230 to one or more remote computers, such as a server computing device 1210 .

[0086] In some embodiments, server 1210 may be an edge server that receives client requests and coordinates the fulfillment of those requests through other servers (such as servers 1220A-C). A server computing device (not shown) may include a computing system such as device 1100 ( Figure 11 ). Although each server computing device (not shown) can logically be a single server, each server computing device (not shown) can be a distributed computing environment encompassing multiple computing devices located at the same physical location or at geographically different physical locations. In some embodiments, each server 1220 corresponds to a group of servers.

[0087] The client computing device 1205 and the server computing devices 1210 and 1220 can each act as a server or client to the other server / client devices. Server 1210 can be connected to a database 1215. Servers 1220A-C can each be connected to a corresponding database 1225A-C. As discussed above, each server 1220 can correspond to a group of servers, and each of these servers can share a database or can have its own database. Databases 1215 and 1225 can store (e.g., store) information such as raw data (e.g., related to patient hemodynamic parameters, three-dimensional representations, CFD representations, representations), algorithms (e.g., derived hemodynamic parameters, digital three-dimensional representations, CFD representations, representations), other patient information, and / or implement the above-mentioned Figure 1-11 Although databases 1215 and 1225 are logically shown as a single unit, each of databases 1215 and 1225 can be a distributed computing environment encompassing multiple computing devices, which can be located within their corresponding servers, or can be located at the same physical location or at geographically different physical locations.

[0088] The network 1230 can be a local area network (LAN) or a wide area network (WAN), but can also be other wired or wireless networks. The network 1230 can be the Internet or some other public or private network. The client computing device 1205 can be connected to the network 1230 through a network interface (such as, through wired or wireless communication). Although the connection between the server 1210 and the server 1220 is shown as a separate connection, these connections can be any type of local, wide area, wired or wireless network, including the network 1230 or a separate public or private network.

[0089] III. Renal Neuromodulation

[0090] Renal neuromodulation is the partial or complete incapacitation or other effective destruction of renal nerves (e.g., nerves that terminate in the kidney or in a structure closely associated with the kidney). In particular, renal neuromodulation can include inhibiting, reducing, and / or blocking neural communication along the nerve fibers (e.g., efferent and / or afferent nerve fibers) of the kidney. Such incapacitation can be long-term (e.g., permanent or for a period of months, years, or decades) or short-term (e.g., for a period of minutes, hours, days, or weeks). It is expected that renal neuromodulation contributes to a systemic reduction in sympathetic tone or impulses and / or benefits at least some specific organs and / or other body structures that are innervated by the sympathetic nerves. Therefore, it is expected that renal neuromodulation can be used to treat clinical conditions associated with systemic sympathetic overactivity or hyperactivity, particularly conditions associated with central sympathetic overstimulation. For example, renal neuromodulation is expected to be effective in treating conditions such as hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, polycystic kidney disease, polycystic ovary syndrome, osteoporosis, erectile dysfunction, and sudden death.

[0091] During the treatment process, renal neuromodulation can be induced electrically, thermally, chemically, or in other suitable ways or combinations at one or more suitable treatment areas. The treatment area can be located within or otherwise close to the renal lumen (e.g., renal artery, ureter, renal pelvis, renal calyces, renal calyces, or other suitable structures) and the treated tissue can include perivascular tissue (at least close to the renal lumen wall). For example, with respect to the renal artery, the treatment process can include regulating the nerves in the renal plexus, which are closely located within or adjacent to the adventitia of the renal artery.

[0092] Renal neuromodulation can include a cryotherapy mode alone or in combination with another treatment mode. Cryotherapy can include cooling the tissue at the treatment area in a manner that regulates neural function. For example, sufficient cooling of at least a portion of the renal sympathetic nerves can slow or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity. This effect can occur due to cryotherapy tissue damage, which can include, for example, direct cell damage (e.g., necrosis), vascular or luminal damage (e.g., by destroying the supply blood vessels so that cells die from lack of nutrients), and / or sublethal hypothermia with subsequent apoptosis. Exposure to cryotherapy can result in acute cell death (e.g., death immediately after exposure) and / or delayed cell death (e.g., death during tissue thawing and subsequent hyperperfusion). Neuromodulation using cryotherapy according to embodiments of the present technology can include cooling structures close to the inner surface of the body cavity wall so that the tissue is effectively cooled to the depth where the renal sympathetic nerves reside. For example, in some embodiments, the cooling component of the cryotherapy device can be cooled to the extent that it causes therapeutically effective low-temperature renal neuromodulation. In other embodiments, the cryotherapy mode can include cooling that is configured not to cause neuromodulation. For example, the cooling can be at or above certain cryogenic temperatures and can be used to control neuromodulation via another treatment mode (e.g., to protect tissue from neuromodulation energy).

[0093] Renal neuromodulation can include an electrode-based or transducer-based treatment mode alone or in combination with another treatment mode. Electrode-based or transducer-based treatment can include delivering electricity and / or another form of energy to the tissue at the treatment location so as to stimulate and / or heat the tissue in a manner that regulates neural function. For example, fully stimulating and / or heating at least a portion of the renal sympathetic nerves can slow down or possibly block the conduction of nerve signals to produce a long-term or permanent reduction in renal sympathetic nerve activity. Various suitable types of energy can be used to stimulate and / or heat the tissue at the treatment location. For example, neuromodulation according to an embodiment of the present technology can include delivering RF energy, pulsed electrical energy, microwave energy, light energy, focused ultrasound energy (e.g., high-intensity focused ultrasound energy), or another suitable type of energy, alone or in combination. The electrodes or transducers used to transmit this energy can be used alone or in combination with other electrodes or transducers in a multi-electrode or multi-transducer array. In addition, energy can be applied from within the body (e.g., within the vascular system or other body cavity in a catheter-based approach) and / or from outside the body (e.g., via an applicator located outside the body). Furthermore, when target tissue adjacent to non-target tissue is subjected to neuromodulatory cooling, the energy can be used to reduce damage to the non-target tissue.

[0094] Neuromodulation using focused ultrasound energy (e.g., high-intensity focused ultrasound energy) may be beneficial relative to neuromodulation using other treatment modalities. Focused ultrasound is an example of a transducer-based treatment modality that can be delivered from outside the body. Focused ultrasound therapy can be performed in close association with imaging (e.g., magnetic resonance imaging, computed tomography, fluoroscopy, ultrasound (e.g., intravascular or intracavitary), optical coherence tomography, or another suitable imaging modality). For example, imaging can be used to identify the anatomical location of the treatment location (e.g., as a set of coordinates relative to a reference point). The coordinates can then be entered into a focused ultrasound device that is configured to vary the power, angle, phase, or other suitable parameters to generate an ultrasound focal zone at a location corresponding to the coordinates. The focal zone can be small enough to localize therapeutically effective heating at the treatment location while partially or completely avoiding potential harmful damage to nearby structures. To generate the focal zone, the ultrasound device can be configured to pass the ultrasound energy through a lens, and / or the ultrasound energy can be generated by a curved transducer or by multiple transducers in a (curved or straight) phased array.

[0095] The heating effects of electrode-based or transducer-based treatments can include ablations, and / or non-ablative changes or damage (e.g., via continuous heating and / or resistive heating). For example, the treatment process can include raising the temperature of the target nerve fibers to a target temperature above a first threshold to achieve non-ablative changes, or above a higher second threshold to achieve ablation. For non-ablative changes, the target temperature can be above about body temperature (e.g., about 37°C) but below about 45°C, and for ablation, the target temperature can be above about 45°C. Heating tissue to a temperature between about body temperature and about 45°C can cause non-ablative changes, for example, via moderate heating of the target nerve fibers or the vascular or luminal structures that perfuse the target nerve fibers. In the event that the vascular structure is affected, the target nerve fibers can refuse perfusion, resulting in necrosis of the neural tissue. Heating tissue to a target temperature above about 45°C (e.g., above about 70°C) can cause ablation, for example, via substantial heating of the target nerve fibers or the vascular or luminal structures that perfuse the target fibers. In some patients, it may be desirable to heat the tissue to a temperature sufficient to ablate target neural fibers or vascular or luminal structures, but below about 40°C (eg, below about 95°C, below about 90°C, or below about 85°C).

[0096] Renal neuromodulation can include chemical-based treatment modalities alone or in combination with another treatment modality. Neuromodulation using chemical-based treatments can include delivering one or more chemicals (e.g., drugs or other agents) to tissue at the treatment site in a manner that modulates neural function. For example, the chemical can be selected to generally affect the treatment site or selectively affect some structures at the treatment site and not others. For example, the chemical can be guanethidine, ethanol, phenol, a neurotoxin, or other suitable agent selected to alter, damage, or destroy nerves. Various suitable techniques can be used to deliver the chemical to the tissue at the treatment site. For example, the chemical can be delivered via one or more needles from outside the body or delivered within the vasculature or other body cavity. In an intravascular example, a catheter can be used to position a treatment element comprising multiple needles (e.g., microneedles) within a blood vessel, which can be retracted or otherwise blocked prior to deployment. In other embodiments, the chemical can be introduced into the tissue at the treatment site via simple diffusion through the wall of the body cavity, electrophoresis, or another suitable mechanism. Similar techniques can be used to introduce chemicals that are configured not to cause neuromodulation but to promote neuromodulation via another treatment modality.

[0097] IV. Related anatomy and physiology

[0098] As previously noted, the sympathetic nervous system (SNS) is a branch of the autonomic nervous system, along with the enteric nervous system and the parasympathetic nervous system. It is always active at a basal level (called sympathetic tone) and becomes more active when stressed. Like the rest of the nervous system, the sympathetic nervous system operates through a series of interconnected neurons. Although many sympathetic neurons are located within the central nervous system (CNS), sympathetic neurons are often considered part of the peripheral nervous system (PNS). Sympathetic neurons of the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal sympathetic neurons connect to peripheral sympathetic neurons through synapses. Therefore, spinal sympathetic neurons are called presynaptic (or preganglionic) neurons, while peripheral neurons are called postsynaptic (or postganglionic) neurons.

[0099] At the synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds to and activates the nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulation, postganglionic neurons primarily release noradrenaline (norepinephrine). Prolonged activation can cause the release of epinephrine from the adrenal medulla.

[0100] Once released, norepinephrine and epinephrine bind to adrenergic receptors on peripheral tissues. Binding to adrenergic receptors results in neural and hormonal responses. Physiological manifestations include pupil dilation, increased heart rate, occasional vomiting, and increased blood pressure. Increased sweating due to binding to cholinergic receptors on sweat glands has also been observed.

[0101] The sympathetic nervous system is responsible for the multistable mechanism in the organism of up-regulation and down-regulation. Fibers from the SNS innervate the tissues in almost every organ system, thereby providing at least some regulatory functions to physiological characteristics as diverse as pupil diameter, intestinal motility and urine output. This reaction is also referred to as the sympathetic adrenal response of the body, because the preganglionic sympathetic nerve fibers (and all other sympathetic nerve fibers) that terminate in the adrenal medulla secrete acetylcholine, which activates the secretion of epinephrine (adrenaline) and norepinephrine (noradrenaline) to a lesser extent. Therefore, directly via the pulsation transmitted by the sympathetic nervous system and indirectly via the catecholamines secreted from the adrenal medulla to mediate this reaction that mainly acts on the cardiovascular system.

[0102] Science generally views the SNS as an autoregulatory system, that is, a system that operates without the intervention of conscious thought. Because the sympathetic nervous system is responsible for priming the body for action, some evolutionary theorists have proposed that the sympathetic nervous system operated in early organisms to maintain survival. An example of such priming is the moment before arousal, when sympathetic outflow spontaneously increases in preparation for action.

[0103] A. Sympathetic nervous system

[0104] like Figure 13 As shown, SNS provides the neural network that allows brain to communicate with body.Sympathetic nerve originates in the spinal column, towards the middle of the spinal cord in the middle lateral cell column (or lateral angle), and it starts from the first thoracic segment of the spinal cord and is considered to extend to the second or third lumbar segment.Because its cell starts from the thoracic vertebra and lumbar vertebra area of ​​the spinal cord, it can be considered that SNS has thoracolumbar outflow.The axons of these nerves leave the spinal cord by anterior root / root.They pass near the spinal column (sensory) ganglion, where they enter the anterior ramus of the spinal nerve.However, different from somatic nerve innervation, they are soon separated by white branch connector, and white branch connector is connected to the paravertebral (near the spinal column) or prevertebral (near the aortic branch) ganglion extending beside the spinal column.

[0105] To reach their target organs and glands, axons must travel long distances in the body, and to accomplish this, many axons relay their message to a second cell via synaptic transmission. The tip of the axon connects to the dendrites of the second cell across a space (the synapse). The first cell (the presynaptic cell) sends a neurotransmitter across the synaptic cleft, where it activates the second cell (the postsynaptic cell). The message is then carried to its final destination.

[0106] In the SNS and other components of the peripheral nervous system, these synapses are produced in areas called ganglia (discussed above). The cells that send their fibers are called preganglionic cells, and the cells whose fibers leave the ganglia are called postganglionic cells. As mentioned above, the preganglionic cells of the SNS are located between the first thoracic (T1) segment and the third lumbar (L3) segment of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to target organs or glands.

[0107] The ganglia include not only the sympathetic trunk but also the cervical ganglia (superior, middle, and inferior), which send sympathetic nerve fibers to the organs of the head and chest, and the celiac and mesenteric ganglia (which send sympathetic nerve fibers to the intestines).

[0108] 1. Innervation of the kidneys

[0109] like Figure 14 As shown in Figure 1, the kidney is dominated by the renal plexus (RP) that is closely associated with the renal artery. The renal plexus (RP) is an autonomic nerve plexus that surrounds the renal artery and is embedded in the adventitia of the renal artery. The renal plexus (RP) extends along the renal artery until it reaches the substance of the kidney. The fibers that contribute to the renal plexus (RP) are produced by the celiac ganglion, superior mesenteric ganglion, aortic renal ganglion and aortic plexus. The renal plexus (RP) (also known as the renal nerve) is mainly composed of sympathetic components. There is no (or at least very little) parasympathetic innervation of the kidney.

[0110] The preganglionic neuron cell body is located in the intermediolateral cell column of the spinal cord. The preganglionic axons pass through the paravertebral ganglia (they do not synapse) to become the lesser splanchnic nerve, the smallest splanchnic nerve, the first lumbar splanchnic nerve, the second lumbar splanchnic nerve, and travel to the celiac ganglion, the superior mesenteric ganglion and the aortic renal ganglion. The postganglionic neuron cell body exits the celiac ganglion, the superior mesenteric ganglion and the aortic renal ganglion to the renal plexus (RP) and is distributed to the renal vascular system.

[0111] 2. Renal sympathetic nerve activity

[0112] Messages flow through social media in a bidirectional manner. Outgoing messages can trigger changes in different parts of the body simultaneously. For example, the sympathetic nervous system can increase heart rate; dilate bronchial passages; reduce bowel motility (movement); constrict blood vessels; increase esophageal motility; cause pupil dilation, piloerection (goose bumps), and perspiration (sweating); and raise blood pressure. Incoming messages carry information from various organs and sensory receptors throughout the body to other organs, particularly the brain.

[0113] Hypertension, heart failure, and chronic kidney disease are some of the many disease states caused by chronic activation of the SNS (particularly the renal sympathetic nervous system). Chronic activation of the SNS is a maladaptive response that drives the progression of these disease states. Drug management of the renin-angiotensin-aldosterone system (RAAS) has been a long-standing method for reducing the overactivity of the SNS, but some are inefficient.

[0114] As mentioned above, the renal sympathetic nervous system has been identified experimentally and in humans as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as, heart failure), and progressive nephropathy. Studies using a radiotracer dilution method to measure norepinephrine efflux from the kidneys to the plasma show that the increased renal norepinephrine (NE) overflow rate (which is consistent with the increased NE overflow from the heart) in patients with essential hypertension (especially in young hypertensive patients) is consistent with the hemodynamic profile typically seen in early hypertension and is characterized by increased heart rate, cardiac output, and renal vascular resistance. It is now known that essential hypertension is typically neurogenic, often with significant sympathetic nervous system overactivity.

[0115] Activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure, as evidenced by the exaggerated increase in NE overflow from the heart and kidneys to the plasma in this patient population. Consistent with this concept is the recent demonstration of a strong negative predictive value of renal sympathetic nerve activation for all-cause mortality and cardiac transplantation in patients with congestive heart failure, independent of overall sympathetic nerve activity, glomerular filtration rate, and left ventricular ejection fraction. These findings support the concept that therapeutic regimens designed to reduce renal sympathetic nerve stimulation have the potential to improve the survival of patients with heart failure.

[0116] Chronic and end-stage renal disease are characterized by elevated sympathetic activation. In patients with chronic and end-stage renal disease, plasma levels of norepinephrine above the median have been shown to be a precursor to all-cause mortality and death from cardiovascular disease. This is also true for patients with diabetes or contrast-induced nephropathy. There is convincing evidence that sensory afferent signals originating from the diseased kidneys are the primary cause of initiation and maintenance of elevated central sympathetic outflow in this patient population; this contributes to the well-known adverse consequences of chronic sympathetic overactivity, such as hypertension, left ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

[0117] (i) Renal sympathetic nerve outflow activity

[0118] Sympathetic nerves to the kidneys terminate in blood vessels, juxtaglomerular apparatus, and renal tubules. Stimulation of the renal sympathetic nerves results in the release of renin, increased sodium (Na + ) reabsorption and the reduction of renal blood flow. These components of the neural regulation of renal function are greatly stimulated in the disease state characterized by elevated sympathetic tone and clearly promoting the increase in blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate caused by renal sympathetic nerve efferent stimulation may be the basis of the loss of renal function in cardiorenal syndrome (which is the renal insufficiency caused by the progressive complications of chronic heart failure), with a clinical course that fluctuates usually with the patient's clinical state and treatment. The pharmacological strategy for hindering the results of renal efferent sympathetic nerve stimulation includes centrally acting sympathetic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to prevent angiotensin II and aldosterone activation caused by renin release) and diuretics (intended to antagonize sodium and water retention mediated by renal sympathetic nerves). However, current pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects and other.

[0119] (ii) Renal sensory afferent nerve activity

[0120] The kidneys communicate with the entire structure of the central nervous system via renal sensory afferent nerves. Several forms of "kidney injury" can cause activation of sensory afferent signals. For example, renal ischemia, decreased stroke volume or renal blood flow, or excessive adenosine can trigger activation of afferent nerve communication. Figure 15 and Figure 16As shown in , this afferent communication can be from the kidney to the brain or from one kidney to another (via the central nervous system). These afferent signals are all centrally integrated and may result in increased sympathetic outflow. The sympathetic impulses are directed toward the kidneys, thereby activating the RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic overactivity also affects other organs and body structures (such as the heart and peripheral vasculature) that are innervated by the sympathetic nerves, resulting in the adverse effects of the described sympathetic activation, some aspects of which also contribute to increased blood pressure.

[0121] Thus, physiology suggests that (i) modulation of tissues with efferent sympathetic nerves will reduce inappropriate renin release, sodium retention, and reduce renal blood flow, and (ii) modulation of tissues with afferent sensory nerves will reduce the systemic contribution to hypertension and other disease states associated with central sympathetic tone through its direct effects on the posterior hypothalamus and the contralateral kidney. In addition to the central hypotensive effects of denervation of the afferent kidneys, a desired reduction in central sympathetic outflow to various other sympathetically innervated organs, such as the heart and blood vessels, is anticipated.

[0122] B. Additional Clinical Benefits of Renal Denervation

[0123] As described above, renal denervation may be valuable in the treatment of several clinical conditions characterized by increased global and specific renal sympathetic nerve activity, such as hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death. Because the reduction in afferent nerve signals contributes to a systemic reduction in sympathetic tone / impulsivity, renal denervation may also be beneficial in treating other conditions associated with systemic sympathetic hyperactivity. Thus, renal denervation may also benefit other organs and body structures innervated by the sympathetic nerves, including Figure 13 For example, as previously discussed, reduction of central sympathetic nerve impulses can reduce insulin resistance, which afflicts people with metabolic syndrome and type 2 diabetes. Furthermore, patients with osteoporosis are also sympathetically activated and may also benefit from downregulation of sympathetic nerve impulses that accompanies renal denervation.

[0124] C. Achieve intravascular access to the renal artery

[0125] According to the present technology, neuromodulation of the left and / or right renal plexus (RP) closely associated with the left and / or right renal arteries can be achieved through intravascular access. Figure 17As shown in Figure 1, the aorta carries blood from the left ventricle of the heart, moved by the heart's contractions. The aorta descends through the chest and branches into the left and right renal arteries. Below the renal arteries, the aorta branches into the left and right common iliac arteries. The left and right common iliac arteries descend through the left and right legs, respectively, and connect to the left and right femoral arteries.

[0126] like Figure 18 As shown, blood collects in the veins and enters the iliac veins through the femoral veins and into the inferior vena cava, returning to the heart. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to deliver blood to the right atrium of the heart. Blood is pumped from the right atrium through the right ventricle into the lungs, where it is oxygenated. From the lungs, the oxygenated blood is transported to the left atrium. From the left atrium, the oxygenated blood is transported through the left ventricle back to the aorta.

[0127] As will be described in more detail later, the femoral artery can be accessed and cannulated only at the base of the femoral triangle below the midpoint of the inguinal ligament. A catheter can be inserted percutaneously through this access area into the femoral artery, through the iliac arteries and aorta, and placed into either the left or right renal artery. This includes providing an intravascular route that provides minimally invasive access to the respective renal artery and / or other renal vessels.

[0128] The wrist, upper arm, and shoulder area provide other locations for introducing a catheter into the arterial system. For example, a catheterization of the radial, brachial, or axillary arteries can be used in selected cases. The catheter introduced via these entry points can use standard angiographic techniques to pass through the subclavian artery on the left side (or via the subclavian and brachiocephalic arteries on the right side), through the aortic arch, down along the descending aorta, and into the renal arteries.

[0129] D. Properties and Characteristics of Renal Vasculature

[0130] Because neuromodulation of the left and / or right renal plexus (RP) can be achieved through intravascular access in accordance with the present technology, the properties and characteristics of the renal vasculature can impose constraints on and / or inform the design of devices, systems, and methods for achieving such renal neuromodulation. Some of these properties and characteristics may vary across patient populations and / or within a particular patient over time, as well as in response to disease states such as hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, etc. As explained herein, these properties and characteristics may be related to the efficacy of the procedure and the specific design of the intravascular device. Properties of interest may include, for example, material / mechanical, spatial, fluid / hemodynamic, and / or thermodynamic properties.

[0131] As discussed above, the catheter can be advanced percutaneously into the left or right renal artery via a minimally invasive intravascular route. However, minimally invasive renal artery access can be challenging, for example, because the renal artery is often extremely tortuous, can be a relatively small diameter, and / or can be a relatively short length compared to some other arteries that are routinely accessed using a catheter. In addition, renal artery atherosclerosis is common in many patients, particularly those suffering from cardiovascular disease. Renal artery anatomy can also vary significantly from patient to patient, which further complicates minimally invasive access. For example, significant inter-patient variation can be seen in relative tortuosity, diameter, length, and / or atherosclerotic plaque load, and the take-off angle of the renal artery from the aorta. Devices, systems, and methods for achieving renal neuromodulation via intravascular access should consider these and other aspects of renal artery anatomy and their variation across patient populations when minimally invasively accessing the renal artery.

[0132] In addition to complicating access to the renal artery, details of the renal anatomy also complicate establishing stable contact between the neuromodulator and the luminal surface or wall of the renal artery. For example, the narrow space within the renal artery and the tortuosity of the artery can hinder navigation. Furthermore, establishing consistent contact can be complicated by patient movement, respiration, and / or the cardiac cycle, as these factors can cause significant movement of the renal artery relative to the aorta, and the cardiac cycle can transiently dilate the renal artery (i.e., cause the wall of the artery to pulsate).

[0133] Even after entering the renal artery and establishing stable contact between the neuromodulator and the artery's luminal surface, the nerves in and around the artery's adventitia should still be safely modulated by the neuromodulator. Effectively applying thermal therapy within the renal artery is nontrivial given the potential clinical complications associated with thermal therapy. For example, the renal artery's intima and media are highly susceptible to thermal damage. As discussed in more detail below, the thickness of the intimal media separating the vessel lumen from its adventitia means that the target renal nerves can be several millimeters from the artery's luminal surface. Sufficient energy should be delivered to the target renal nerves, or heat removed from them, to modulate the target renal nerves without excessively cooling or heating the vessel wall to the point of freezing, drying it out, or otherwise potentially affecting them to an undesirable degree. A potential clinical complication associated with excessive heating is thrombosis caused by coagulation of blood flowing through the artery. Given that such thrombosis could lead to renal infarction, thereby causing irreversible damage to the kidneys, thermal therapy within the renal artery should be applied with caution. Therefore, the complex fluid dynamics and thermodynamic conditions that exist in the renal artery during treatment (particularly those conditions that may affect the dynamics of heat transfer at the treatment area) may be important in applying energy (e.g., heating thermal energy) and / or removing heat from tissue within the renal artery (e.g., cooling thermal conditions).

[0134] Because the location of treatment may also affect clinical efficacy, the neuromodulatory device should also be configured to allow for adjustable positioning and repositioning of the energy delivery element within the renal artery. For example, given that the renal nerves can be spaced axially around the renal artery, it may be attractive to apply circumferential treatment within the renal artery. In some cases, circumferential damage that may result from continuous circumferential treatment may potentially be associated with renal artery stenosis. Therefore, the formation of more complex lesions along the longitudinal dimension of the renal artery and / or the repositioning of the neuromodulatory device to multiple treatment locations may be desirable. However, it should be noted that the benefits of creating circumferential ablations may outweigh the risks of renal artery stenosis, or this risk may be mitigated using certain embodiments or in certain patients, and creating circumferential ablations may be the goal. In addition, variable positioning and repositioning of the neuromodulatory device may prove useful in cases where the renal artery is particularly tortuous or there are proximal branch vessels detaching from the main renal artery vessel, making treatment in certain locations challenging. Manipulation of the device in the renal artery should also take into account the mechanical damage imposed by the device on the renal artery. Movement of the device within the artery, for example by insertion, manipulation, unblocking bends, etc., can result in dissection, perforation, intimal denudation, or disruption of the internal elastic lamina.

[0135] V. Additional Examples

[0136] 1. A system for optimizing neuromodulation therapy, the system comprising:

[0137] A neuromodulation catheter comprising:

[0138] an elongated shaft having a proximal portion and a distal portion, wherein the shaft is configured to position the distal portion intravascularly at a treatment region within a blood vessel of a human patient;

[0139] a neuromodulation assembly at the distal portion of the shaft; and at least one sensor, wherein the sensor is configured to transmit hemodynamic data related to the blood vessel;

[0140] A computing device having a memory and a processor, wherein the memory stores instructions that, when executed by the processor, cause the system to perform operations comprising—

[0141] receiving digital data related to a three-dimensional image of the blood vessel; receiving hemodynamic data from the sensor;

[0142] generating, at the processor, a computational fluid dynamics (CFD) model of the blood vessel based at least in part on the three-dimensional imaging data and the hemodynamic data;

[0143] identifying, based on the CFD model, a target region of the blood vessel suitable for neuromodulation therapy and an avoidance region of the blood vessel less suitable for neuromodulation therapy;

[0144] A representation of the blood vessel including a visual marker indicating the avoidance region is displayed.

[0145] 2. The system of example 1, wherein the blood vessel is a renal blood vessel, a renal artery, a pulmonary artery, a hepatic artery, a coronary artery, or an aorta.

[0146] 3. The system of Example 1, wherein the blood vessel is a main blood vessel, at least one branch blood vessel of the main blood vessel, or at least one accessory blood vessel directly coupled to the at least one branch blood vessel or another blood vessel coupled to the main blood vessel.

[0147] 4. The system of any of the preceding examples, wherein the sensor comprises at least one of a blood pressure sensor or a blood flow sensor.

[0148] 5. The system of any of the preceding examples, wherein the neuromodulation catheter further comprises a transmitter at the distal portion of the shaft, wherein the transmitter is configured to transmit the current position of the neuromodulation component in the blood vessel to a receiver.

[0149] 6. The system of example 5, wherein the transmitter is configured to transmit the position of the neuromodulation catheter in real time.

[0150] 7. A system as in any of the foregoing examples, wherein the memory further stores instructions that, when executed by the processor, cause the system to perform operations including: receiving position data from the neuromodulation catheter related to the position of the neuromodulation catheter in the blood vessel; and providing a recommendation to the user, via the processor, on whether to continue neuromodulation treatment at the device location based on the identified avoidance area.

[0151] 8. The system of example 7, wherein providing the recommendation via the processor comprises generating a signal to the user indicating the avoidance area, wherein the signal comprises an audio signal, a visual signal, a tactile signal, or a combination thereof.

[0152] 9. The system of Example 7, wherein providing the recommendation further includes: recommending avoiding neuromodulation therapy at one or more portions of the blood vessel, wherein the one or more portions have at least one hemodynamic parameter in the hemodynamic data that exceeds a threshold hemodynamic parameter and thereby indicates at least one local blood flow abnormality.

[0153] 10. The system of any of the preceding examples, wherein displaying the representation of the blood vessel further comprises displaying a marker of a target region of the blood vessel for delivery of neuromodulation therapy.

[0154] 11. The system of any of the preceding examples, wherein displaying the representation of the blood vessel further comprises: displaying a first portion of the blood vessel on the representation; and displaying a second portion of the blood vessel on the representation, wherein the second portion corresponds to one or more avoidance regions of the blood vessel, and wherein the displayed first portion has a lower resolution than the displayed second portion.

[0155] 12. The system of any of the preceding examples, wherein receiving the hemodynamic data comprises receiving data related to blood pressure, blood flow, and / or blood impedance.

[0156] 13. The system of any of the preceding examples, wherein the at least one sensor is at the distal portion of the shaft.

[0157] 14. The system of any one of examples 1 to 12, further comprising a guidewire having the at least one sensor.

[0158] 15. The system of any of the preceding examples, wherein receiving the digital data related to three-dimensional imaging of the blood vessel comprises receiving data acquired using angiography, x-ray imaging, computed tomography (CT), MRI, or a combination thereof.

[0159] 16. The system of any of the foregoing examples, wherein receiving hemodynamic data comprises receiving blood pressure data and / or blood flow data measured at a location within a primary portion of the blood vessel having at least generally laminar flow; or, wherein receiving hemodynamic data comprises receiving blood pressure data and / or blood flow data measured at a location within at least one branch vessel and / or at least one accessory vessel.

[0160] 17. The system of any of the preceding examples, wherein identifying the avoidance region of the blood vessel comprises identifying portions of the blood vessel at or near an ostium, carina, conical region, calcification, fibromuscular dysplasia, aneurysm, bifurcation, or a combination thereof.

[0161] 18. The system of any of the preceding examples, wherein generating the computational fluid dynamics model of the blood vessel comprises applying hemodynamic parameters derived from empirical or synthetic data.

[0162] 19. A system as in any of the preceding examples, wherein the memory further stores instructions that, when executed by the processor, cause the system to perform operations comprising: displaying the CFD representation of the blood vessel on a user interface, the CFD representation including visual markings designating an identified target region and an identified avoidance region.

[0163] 20. A system as described in any of the foregoing examples, wherein the memory further stores instructions that, when executed by the processor, cause the system to perform operations including: providing, via the user interface, a recommendation made by the processor regarding whether to continue neuromodulation therapy at the current neuromodulation catheter position within the blood vessel, the recommendation being based on a comparison between the current position of the neuromodulation catheter and an identified target area and / or an identified avoidance area of ​​the blood vessel.

[0164] 21. A system as described in any of the preceding examples, wherein identifying the avoidance areas includes identifying portions of the blood vessel having: low wall shear stress (WSS), high WSS, high WSS gradient, sinus ostia, carina, tapered areas, calcifications, fibromuscular dysplasia, aneurysms, bifurcations, areas of flow separation, vortices, areas of impinging blood flow, areas of turbulent blood flow, areas of secondary blood flow, or a combination thereof.

[0165] 22. A method of assessing a blood vessel for neuromodulation therapy, the method comprising:

[0166] receiving, at a processor, digital data related to a three-dimensional image of the blood vessel;

[0167] receiving, at the processor, hemodynamic data relating to the blood vessel;

[0168] generating, at the processor, a computational fluid dynamics (CFD) model of the blood vessel based at least in part on the imaging data and the hemodynamic data;

[0169] identifying, with reference to the CFD model, an avoidance region of the blood vessel for neuromodulation therapy, wherein the avoidance region comprises a region having at least one of flow separation, vortex formation, flow impingement, low wall shear stress (WSS), or high WSS gradient; and

[0170] A representation of the blood vessel including a visual marker indicating the identified avoidance region is displayed on a user interface.

[0171] 23. The method of embodiment 22, wherein the blood vessel is a renal artery, a pulmonary artery, a hepatic artery, a coronary artery, or an aorta.

[0172] 24. The method of Example 22, wherein the blood vessel is a main blood vessel, at least one branch blood vessel of the main blood vessel, or at least one accessory blood vessel directly coupled to the at least one branch blood vessel or another blood vessel coupled to the main blood vessel.

[0173] 25. The method of any one of Examples 22 to 24, wherein providing the recommendation via the processor comprises generating a signal to the user indicating the avoidance area, wherein the signal comprises an audio signal, a visual signal, a tactile signal, or a combination thereof.

[0174] 26. The method of any one of Examples 22 to 25, wherein displaying the representation of the blood vessel further comprises displaying a marker of a target area of ​​the blood vessel for delivery of neuromodulation therapy.

[0175] 27. The method of any of Examples 22-26, wherein displaying the representation of the blood vessel further comprises:

[0176] displaying a first portion of the blood vessel on the representation; and

[0177] A second portion of the blood vessel is displayed on the representation, wherein the second portion corresponds to one or more avoidance regions of the blood vessel, and wherein the displayed first portion has a lower resolution than the displayed second portion.

[0178] 28. The method of any of Examples 22-27, wherein receiving the hemodynamic data comprises receiving data related to blood pressure, blood flow, and / or blood impedance.

[0179] 29. The method of any of Examples 22 to 27, wherein receiving the hemodynamic data comprises receiving blood pressure data via an external pressure cuff and / or receiving blood flow data via magnetic resonance imaging (MRI), a non-invasive ultrasonic Doppler shift flowmeter, or a combination thereof.

[0180] 30. The method of any of Examples 22 to 29, wherein receiving the digital data related to three-dimensional imaging of the blood vessel comprises receiving data acquired using angiography, x-ray imaging, computed tomography (CT), MRI, or a combination thereof.

[0181] 31. The method of any of examples 22 to 27, wherein receiving hemodynamic data comprises receiving blood pressure data and / or blood flow data measured at a location within a major portion of the blood vessel having at least generally laminar flow;

[0182] 32. The method of any one of Examples 22 to 31, wherein providing the recommendation further comprises:

[0183] A recommendation is made to avoid neuromodulation therapy at one or more portions of the blood vessel having at least one hemodynamic parameter in the hemodynamic data that exceeds a threshold hemodynamic parameter and thereby indicates at least one local blood flow abnormality.

[0184] 33. The method of any of Examples 22 to 32, wherein identifying the avoidance region of the blood vessel comprises identifying portions of the blood vessel at or near an ostium, a carina, a tapered region, calcifications, fibromuscular dysplasia, an aneurysm, a bifurcation, or a combination thereof.

[0185] 34. The method of any one of Examples 22 to 33, wherein generating the computational fluid dynamics model of the blood vessel comprises applying hemodynamic parameters derived from empirical or synthetic data.

[0186] 35. A method of optimizing neuromodulatory therapy in a blood vessel of a human patient, the method comprising:

[0187] receiving, at a processor, digital data related to a three-dimensional image of the blood vessel;

[0188] receiving, at the processor, hemodynamic data associated with the blood vessel;

[0189] generating, at the processor, a computational fluid dynamics (CFD) representation of the blood vessel based at least in part on the imaging data and the hemodynamic data, the computational fluid dynamics representation including flow parameters;

[0190] identifying, via the processor, a target region of the blood vessel suitable for neuromodulation therapy and an avoidance region of the blood vessel less suitable for neuromodulation therapy; and

[0191] The CFD representation of the blood vessel is displayed on a user interface, the CFD representation including visual markings designating the identified target region and the identified avoidance region.

[0192] 36. The method of Example 35, wherein identifying the avoidance area includes identifying portions of the blood vessel having: low wall shear stress (WSS), high WSS, high WSS gradient, sinus ostia, bulges, tapered areas, calcifications, fibromuscular dysplasia, aneurysms, bifurcations, areas of flow separation, vortices, areas of impinging blood flow, areas of turbulent blood flow, areas of secondary blood flow, or a combination thereof.

[0193] 37. The method of Example 35 or Example 36, wherein the sensor disposed within the blood vessel is a sensor of the neuromodulation catheter.

[0194] 38. A non-transitory computer-readable memory storing instructions that, when executed by a processor of a computing device, cause the computing device to perform operations for identifying a target neuromodulation treatment zone in a blood vessel, the operations comprising:

[0195] receiving data related to three-dimensional imaging of the blood vessel;

[0196] receiving at least one of blood pressure data or blood flow data associated with the blood vessel;

[0197] generating a computational fluid dynamics (CFD) model of the blood vessel based at least in part on the blood vessel imaging data and the blood pressure and / or the blood flow data;

[0198] identifying a target region of the blood vessel suitable for neuromodulation therapy and a keep-away region of the blood vessel to be avoided during neuromodulation therapy, the identification being based on the CFD model of the blood vessel;

[0199] And a representation of the blood vessel including visual markings indicating the identified target area and / or the identified avoidance area is displayed on a user interface.

[0200] VI. Conclusion

[0201] The present disclosure is not intended to be exhaustive or to limit the present technology to the precise form disclosed herein. Although specific embodiments of the present technology are described herein for illustrative purposes, various equivalent modifications are possible without departing from the present technology, as will be appreciated by those skilled in the relevant art. In some cases, well-known structures and functions are not shown and / or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present technology. Although the steps of the method may be presented in a particular order herein, in alternative embodiments, these steps may have another suitable order. Similarly, certain aspects of the present technology disclosed in the context of a particular embodiment may be combined or eliminated in other embodiments. In addition, although the advantages associated with these embodiments may be disclosed in the context of certain embodiments, other embodiments may also exhibit such advantages, and not all embodiments must exhibit these advantages or other advantages disclosed herein to fall within the scope of the present technology. Therefore, the present disclosure and related art may encompass other embodiments not explicitly shown and / or described herein.

[0202] Several embodiments of the disclosed technology are described above with reference to the accompanying drawings. The computing device on which the described technology can be implemented may include one or more central processing units, memories, input devices (e.g., keyboards and pointing devices), output devices (e.g., display devices), storage devices (e.g., disk drives), and network devices (e.g., network interfaces). Memories and storage devices are computer-readable storage media that can store instructions that implement at least a portion of the described technology. In addition, data structures and message structures can be stored or transmitted via data transmission media (such as signals on a communication link). Various communication links can be used, such as the Internet, a local area network, a wide area network, or a point-to-point dial-up connection. Therefore, computer-readable media may include computer-readable storage media (e.g., "non-transient" media) and computer-readable transmission media.

[0203] Throughout this disclosure, unless the context clearly indicates otherwise, the singular terms "a / an" and "the" include plural referents. Similarly, when quoting a list with two or more items, unless the word "or" is clearly limited to represent only a single item and does not include other items, the use of "or" in such a list will be interpreted as including (a) any single item in the list, (b) all items in the list, or (c) any combination of items in the list. In addition, throughout this disclosure, the terms "including" and the like are used to refer to including at least the described feature(s), thereby not excluding any larger number of the same feature(s) and / or other features of the additional type. Directional terms such as "upper", "lower", "front", "back", "vertical" and "horizontal" can be used herein to express and clarify the relationship between each element. It should be understood that such terms do not represent absolute orientation. Reference herein to "one embodiment", "embodiment" or similar expressions means that the specific features, structures, operations, or characteristics described in conjunction with the embodiment can be included in at least one embodiment of the present technology. Therefore, the appearance of these phrases or expressions herein does not necessarily refer to the same embodiment. Furthermore, the particular features, structures, operations, or characteristics may be combined in any suitable manner in one or more embodiments.

Claims

1. A system for optimizing neuromodulation therapy, comprising: a processor configured to: receiving digital data related to a three-dimensional image of a patient's blood vessel, the digital data including information about at least one characteristic of the patient's blood vessel; receiving hemodynamic data from at least one sensor; generating a computational fluid dynamics model of the blood vessel based at least in part on the digital data and the hemodynamic data; identifying, based on the computational fluid dynamics model, at least one of a target region of the blood vessel suitable for neuromodulation therapy or an avoidance region of the blood vessel less suitable for neuromodulation therapy; and An output is generated that indicates at least one of the target area or the avoidance area.

2. The system according to claim 1, wherein The at least one characteristic of the blood vessel includes at least one of: a cross-sectional area of ​​the blood vessel, a cross-sectional diameter of the blood vessel, a volume of a portion of the blood vessel, or a length of a portion of the blood vessel.

3. The system according to claim 1, wherein: The at least one feature of the blood vessel comprises at least one of a vessel wall, a portion of the vessel wall, a lumen, a branch, a bifurcation, a carina, an ostium, a tapered region, an aneurysm, a fibromuscular dysplasia, an occlusion, an impingement, a calcification, or an intimal deposit.

4. The system according to claim 1, wherein: The digital data includes data acquired using at least one of: X-ray imaging, computed tomography, magnetic resonance imaging, fluoroscopy, ultrasound, or optical coherence tomography (OCT).

5. The system according to claim 1, wherein: The digital data includes data acquired using angiography.

6. The system according to claim 1, wherein: The hemodynamic data includes a measurement of at least one of blood pressure, blood flow, blood impedance, or blood viscosity of the patient.

7. The system according to claim 1, wherein: Further included is a neuromodulation catheter comprising a sensor of the at least one sensor.

8. The system according to claim 1, wherein: Further included is an external device comprising a sensor of the at least one sensor.

9. The system according to claim 1, wherein: The processor is configured to identify the target region based on the computational fluid dynamics model.

10. The system according to claim 9, wherein The processor is configured to identify the target region by at least comparing a hemodynamic parameter at a given location within the blood vessel with a threshold value.

11. The system according to claim 1, wherein: The processor is configured to identify the avoidance zone based on the computational fluid dynamics model.

12. The system according to claim 11, wherein The processor is configured to identify the avoidance zone by at least comparing a hemodynamic parameter at a given location within the blood vessel with a threshold value.

13. The system according to claim 11, wherein: The processor is configured to identify the avoidance areas by identifying at least portions of the blood vessel having: low wall shear stress (WSS), high WSS, high WSS gradient, ostia, carina, tapered areas, calcifications, fibromuscular dysplasia, aneurysms, bifurcations, areas of flow separation, vortices, areas of impinging blood flow, areas of turbulent blood flow, areas of secondary blood flow, or a combination thereof.

14. The system of claim 1, wherein: Generating the output includes displaying a representation of the blood vessel including a visual marker indicating at least one of the target region or the avoidance region.

15. The system of claim 1, wherein: The processor is configured to: receiving data from a neuromodulation catheter related to a position of the neuromodulation catheter in the blood vessel; Based on the at least one of the avoidance zone or the target zone, a recommendation is output as to whether to continue neuromodulation therapy at the location.

16. A computer-readable storage medium comprising instructions stored thereon, which, when executed by a processor, cause the processor to perform a method comprising the steps of: receiving digital data related to a three-dimensional image of a patient's blood vessel, the digital data including information about at least one characteristic of the patient's blood vessel; receiving hemodynamic data from sensors; generating a computational fluid dynamics model of the blood vessel based at least in part on the digital data and the hemodynamic data; identifying, based on the computational fluid dynamics model, at least one of a target region of the blood vessel suitable for neuromodulation therapy or an avoidance region of the blood vessel less suitable for neuromodulation therapy; and An output is generated that indicates at least one of the target area or the avoidance area.

17. The computer-readable storage medium of claim 16, wherein: Identifying at least one of the target area or the avoidance area includes: identifying the avoidance area by identifying portions of the blood vessel having the following based at least on the computational fluid dynamics model of the blood vessel: low wall shear stress (WSS), high WSS, high WSS gradient, sinus ostia, carina, tapered area, calcification, fibromuscular dysplasia, aneurysm, bifurcation, area of ​​blood flow separation, vortex, area of ​​impinging blood flow, area of ​​turbulent blood flow, area of ​​secondary blood flow, or a combination thereof.

18. A system for optimizing neuromodulation therapy, comprising: a memory configured to store a computational fluid dynamics model of a blood vessel, the computational fluid dynamics model generated based on digital data and sensed hemodynamic data, the digital data relating to a three-dimensional imaging of a patient's blood vessel and including information regarding at least one characteristic of the patient's blood vessel; as well as A processor is configured to identify an avoidance region for neuromodulation therapy based on the computational fluid dynamics model, wherein the avoidance region comprises a region of the blood vessel having at least one of: a localized flow abnormality, a physiological characteristic, or a pathological characteristic.

Images