TWI781077B - Systems and methods for flow stagnation control - Google Patents

Abstract

The present disclosure describes flow stagnation control components that allow improved flow control in systems including injection members, while also limiting the creation of regions of little to no flow in the vasculature, resulting in low flow zones or dead zones. The flow stagnation control components can be formed as an imposed minimum conductance component or a controlled flow partitioning system.

Description

System and method for flow fouling control

In the design of intravascular catheters, occlusive devices are often used to control or block flow in an artery or vein. In some cases, however, occluding flow in an artery or vein creates an area of stagnant or no-flow zone (ie, also referred to as a "dead zone") in which blood does not move. In some instances, the chronic creation of a dead zone in the bloodstream can increase the risk of developing a thrombus or clot, which can be associated with an increased risk of embolism in the patient.

The present invention provides exemplary systems, devices, devices and methods that allow control of blood flow in a portion of an artery or vein to control the occurrence and duration of low-flow or no-flow regions (including dead regions) in a portion of a vessel. In particular, the exemplary systems, methods, devices, and apparatus allow for the control of flow fouling through the use of an additional minimal conduction component or a controlled shunt system.

In one example, the systems, devices, devices and methods use an additional minimal conductive member coupled to a catheter, injector member or other instrument to control the flow rate of blood flow in an artery or vein to control low Occurrence and duration of flow or no-flow regions (including dead regions).

In one example, the systems, devices, devices, and methods are structured to calculate the pressure of the catheter, injector, or other instrument based on sensor measurements from at least two pressure sensors coupled to the catheter, injector member, or other instrument. The vascular portion surrounding a part of a component or other instrument The conductance values are divided and the occurrence and duration of low-flow or no-flow regions (including dead regions) are controlled based on these calculated conductance values.

Exemplary systems, devices, and devices may include an outer loop and an additional minimal conductive component. The extracorporeal circuit comprises: a port for returning blood from the extracorporeal circuit to a vessel in a region of the body; and at least one injector member configured to cause blood to be injected in a vessel point flow. The at least one injector member includes a lumen and a distal tip. The additional minimal conductive element is disposed proximal to the distal tip of the at least one injector member.

Exemplary systems, devices, and apparatus can be structured to implement a method using an additional minimal conductive member. The method includes coupling an outer circuit to a portion of a body. The extracorporeal circuit comprises: a port for returning blood from the extracorporeal circuit to a vessel in a region of the body; and at least one injector member configured to cause blood to be injected in a vessel point flow. The at least one injector member includes a lumen and a distal tip. An additional minimal conductive element is disposed proximal to the distal tip of the at least one injector member. The method further comprises causing an infused flow from the at least one injector member to be at a flow rate such that a net or average retrograde or downstream flow rate above a predetermined minimum flow rate is maintained in the vessel external to the at least one injector member middle.

Exemplary systems, devices, and devices may include an external loop and a controlled shunt system. The extracorporeal circuit includes: a port for returning blood from the extracorporeal circuit to a vessel in a region of the body; and an injector member configured to cause blood to flow at a vascular infusion point flow everywhere. The at least one injector member includes a lumen and a distal tip. The control shunt system comprises: a first pressure sensor for measuring a first parameter indicative of flow at the proximal end of a distal tip of the injector member; a second pressure sensor for measuring for measuring a second parameter indicative of flow, the second sensor being disposed at the proximal end of the injector member at a predetermined distance from the proximal end of the distal tip; and an injection flow rate source, the coupled to the extracorporeal loop to cause the infusion flow to be at a predetermined Constant flow rate mode.

Exemplary systems, devices, and apparatus can be configured to implement a method using a control shunt system. The method includes coupling an outer circuit to a portion of a body. The extracorporeal circuit includes: a port for returning blood from the extracorporeal circuit to a vessel at a region of the body; and an injector member coupled to the port. The injector member includes a distal tip and a shaft having a lumen. The control shunt system comprises: at least one first pressure sensor disposed proximally of the distal tip; at least one second pressure sensor disposed on an outer surface of the shaft of the injector member and an injection flow rate source coupled to the injection member to control a fluid flow from the distal tip of the injector member. The method comprises, during a time interval T, controlling the flow of fluid injected at the distal tip of the injector member to a predetermined flow rate pattern using the injection flow rate source; during the time interval T, using the first the pressure sensor and the second pressure sensor record pressure measurements; and using the data indicative of the pressure measurements and the predetermined flow rate pattern, calculate a proximal external conductance at the distal tip of the injector member or a value for a distal external conduction.

Exemplary systems, devices, and devices may include an external loop, a control shunt system, and a console. The extracorporeal circuit may comprise: a port for returning blood from the extracorporeal circuit to a vessel at a region of the body; and an injector member comprising a distal tip. The control shunt system comprises: a first pressure sensor disposed at the proximal end of the distal tip of the at least one injector member; a second pressure sensor spaced apart from the proximal end of the distal tip A predetermined spacing is disposed at an outer surface of the at least one injector member; and an injection flow rate source coupled to the injection member to control the flow rate of fluid from the distal tip to a predetermined flow rate pattern. The console comprises at least one processing unit programmed to receive, within a time interval T, an indication to use the blood flow with the blood flow injected at the distal tip according to the predetermined flow rate pattern Data from pressure measurements made by the first pressure sensor and the second pressure sensor; and using data indicative of the pressure measurements and the predetermined flow rate pattern, calculating the distance of the at least one injector member At least one of a proximal external conduction or a distal external conduction at the tip of the tip.

Exemplary systems, devices, and apparatus can be structured to implement a method that includes an integral outer loop. The extracorporeal circuit includes: a port for returning blood from the extracorporeal circuit to a vessel at a region of the body; an injector member coupled to the port, the injector member comprising a a distal tip and a shaft having a lumen; at least one first pressure sensor disposed proximally of the distal tip; at least one second pressure sensor disposed on the shaft of the injector member and an injection flow rate source coupled to the injector member to control a fluid flow from the distal tip of the injector member. The method includes coupling the extracorporeal circuit to a body part; controlling the flow of fluid injected at the distal tip of the injector member to a predetermined flow using the infusion flow rate source during a first time interval T1 rate mode; within the first time interval T1, record pressure measurements using the first pressure sensor and the second pressure sensor; using data indicative of the pressure measurements and the predetermined flow rate mode, calculate A value of a proximal external conductance at the distal tip of the injector member; using the first and second pressure measurements and the calculated proximal external conductance to calculate an external flow rate, and using the external flow rate to calculate the ratio of infused flow rate to external flow rate in the distal mixing fluid; and to control the amount of drug or agent added to the infused fluid and adjust using the calculated ratio of infused flow rate to external flow rate The amount to achieve a specified concentration of drug or agent in the mixed distal fluid.

It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in more detail below (provided such concepts are not mutually inconsistent) are considered part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered part of the inventive subject matter disclosed herein. It should also be understood that terminology explicitly employed herein that also may appear in any disclosure incorporated by reference should be accorded a meaning that best corresponds to the particular concepts disclosed herein.

100: catheter system

101: shaft/shaft holding device/shaft device

102: plane

103: Blocking components

200: extracorporeal loop

203: Blocking components

205: dead area

206: Pump system

208: heat exchanger

210:Injector component

212: Vascular injection point

214: blood

216: inject fluid

320: lumen

321: Components/soft airbags

324: Positive new flush flow

326: Back flush flow

328: blood flow

421:Component

424: Backwash flow

426: Positive Flush Flow

428: blood flow

430: hole/orifice

431: hole/aperture

440: spring driven membrane

442: Fluid flow

450: Multi-leaf soft airbag

455: Double leaf soft airbag

460: Gap

465: Three leaf soft airbag

470: Gap

510: Bias valve

521: Components/soft airbags

532: Bias valve

534: flow

538: blood flow

540: Bias valve

542: bypass lumen

548: blood flow

610: first pressure sensor

610': pressure sensor

612: Second pressure sensor

612': pressure sensor

614: injector member/insert member/inner shaft

615: blood flow

616: Flow rate source

617: blood flow

618: Outer shaft

620: Conduit member/conduit

622:near end port

700: In Vitro Systems

700': In vitro systems

700": In vitro system

710: Aortic Vein-Arterial (VA) Extracorporeal Circuit

711: the first port

712: pump

713: Oxygenator

714: Main loop oxygenator/heat exchanger

715: the second port

716: Displacement or volume driven pumps

718:Area injector branch

720: heat exchanger

721: The third port

722: Distal injector component

724: area

726: plus minimum conductive components

728: Coupled pressure sensor pair

800: Exemplary Extracorporeal Loop System

802: console

810: Aortic Vein-Arterial (VA) Extracorporeal Circuit

811: the first port

812: pump

813: Oxygenator

814: heat exchanger

815: the second port

816: Displacement or volume driven pumps

818: branch

820: heat exchanger

821: The third port

822: Distal injector component

826: plus minimum conductive components

828: Pressure sensor pair

850: system

852: console

860: Flow rate control source

862: Reservoir

872: Distal injector component

876: plus minimum conductive components

878: Pressure sensor pair

905: Console

907: processing unit

909: Memory

911: display unit

1002: step

1004: step

1006: step

1052:Step

1054:step

1056:step

1058:step

1060: step

1110: computing device

1112': Processor

1114: core

1114': Core

1118:Multi-touch interface

1120: pointing to the device

1124: virtual machine

1126: operating system

1132: Network device

1134: storage device

1140:Software application

F _b : flow rate/fluid/flow/blood flow

F _tip : flow rate/fluid/flow/blood flow

G ₀ : fluid conduction

G _b : proximal conduction

G _tip : distal conduction

l : discrete length

Pa: pressure

Pb: pressure

_Pin : pressure

P _out : pressure

P _tip : pressure

△: Predefined spacing

Δt: time period

Those of ordinary skill will appreciate that the drawings are primarily for illustration purposes and are not intended to be limiting The scope of the subject matter of the invention described herein. The drawings are not necessarily to scale; in some instances, various aspects of the inventive subject matter disclosed herein may be shown exaggerated or enlarged in the drawings to facilitate understanding of one of the various features. In the drawings, similar reference characters typically identify similar features (eg, functionally similar and/or structurally similar elements).

Figure 1A shows a schematic diagram of one exemplary catheter system in accordance with the principles of the present invention.

1B-1C show exemplary diagrams of fluid conduction in vascular spaces across boundaries.

Figure 2A shows an exemplary extracorporeal circuit according to the principles of the invention.

2B-2C show schematic diagrams of another catheter system in accordance with the principles of the present invention.

3A-3B show an example of another catheter system in accordance with the principles of the invention.

4A-4B show an example of another catheter system in accordance with the principles of the invention.

Figure 4C shows an example of another catheter system in accordance with the principles of the present invention.

Figures 4D(i) and 4D(ii) show an example of another catheter system in accordance with the principles of the present invention.

5A(i) and 5A(ii) show an example of an offset valve on a bore in an exemplary catheter system in accordance with the principles of the present invention.

5B shows an example of an offset valve on an aperture in an exemplary catheter system in accordance with the principles of the invention.

5C shows an example of a biased valve on an aperture in an exemplary catheter system in accordance with the principles of the invention.

Figure 6A shows an exemplary injector member coupled to a pressure sensor in an exemplary catheter system in accordance with the principles of the present invention.

6B shows another exemplary injector member coupled to a pressure sensor in an exemplary catheter system in accordance with the principles of the present invention.

Figure 6C shows an exemplary catheter coupled to a pressure sensor in accordance with the principles of the present invention.

Figure 6D shows another exemplary catheter coupled to a pressure sensor in accordance with the principles of the present invention.

Figure 7A shows an exemplary extracorporeal circuit system according to the principles of the present invention.

Figure 7B shows another exemplary extracorporeal circuit system according to the principles of the present invention.

Figure 7C shows another exemplary extracorporeal circuit system according to the principles of the present invention.

Figure 8A shows an exemplary extracorporeal loop system coupled to a console in accordance with the principles of the present invention.

8B shows another exemplary extracorporeal loop system coupled to a console in accordance with the principles of the present invention.

Fig. 9 is a block diagram showing an exemplary computing device in accordance with the principles of the present invention.

10A-10B show flowcharts illustrating exemplary methods in accordance with the principles of the invention.

Fig. 11 is a block diagram of an exemplary computing device in accordance with the principles of the present invention.

The following are concepts pertaining to systems, devices, devices and methods that allow control of blood flow in a portion of an artery or vein to control the occurrence and duration of low-flow or no-flow regions (including dead regions) in a portion of a vessel and a more detailed description of its examples. Exemplary systems, methods, devices, and devices that allow for control of at least two regions of selective thermal treatment are also described. It should be appreciated that the various concepts introduced above and discussed in greater detail below can be implemented in any of numerous ways, as the disclosed concepts are not limited to any particular implementation. Examples of specific implementations and applications are provided primarily for purposes of illustration.

As used herein, the term "include" means including but not limited to, and the term "including" means including but not limited to. The term "based on" means based at least in part on.

With respect to surfaces described herein in connection with various examples of the principles herein, any reference to a "top" surface and a "bottom" surface is primarily intended to indicate that the various elements/components are The relative position, alignment and/or orientation of the plates and each other, and these terms do not necessarily denote any particular frame of reference (eg, a gravitational frame of reference). Thus, reference to a "bottom" of a surface or layer does not necessarily require that the indicated surface or layer be facing the ground. Similarly, terms such as "above", "below", "above", "underneath", etc. do not necessarily refer to any particular frame of reference (such as a gravitational frame of reference), but are instead primarily used to refer to various elements/components relative to a surface. and their relative position, alignment and/or orientation to each other.

The terms "disposed on" and "disposed over" encompass the meaning of "embedded in" (including "partially embedded in"). Further, references to feature A being "disposed on," "disposed between" or "disposed over feature B" encompass instances where feature A is in contact with feature B and where other layers and/or other components An instance positioned between feature A and feature B.

As used herein, the term "proximal" refers to a direction toward a portion of a catheter, an injector member, or other instrument (such as, but not limited to, a grip or other handle) that a user will manipulate. As used herein, the term "distal" refers to a direction away from the handle or other handle of the catheter, injector member, or other instrument. For example, the tip of the injector member is disposed at a distal portion of the injector member.

During certain procedures using a catheter, blood flow to a vein or an artery may be occluded. No-flow or low-flow regions, including dead regions, can occur in portions of a vessel whenever blood flow is at least partially blocked. For example, an intravascular catheter or other similar device may include an occlusive device for controlling or blocking flow in an artery or vein. In certain instances, occluding blood flow in an artery or vein can create regions of markedly reduced blood flow, or no-flow zones, where blood is substantially stagnant. These regions are referred to herein as "dead regions" or "no-flow regions." If no-flow or low-flow regions (including dead areas) persist for prolonged periods of time, the tissue may lack blood flow and may be damaged. In some instances, the chronic creation of a dead zone in the bloodstream can increase the risk of developing a thrombus or clot, which is associated with an increased risk of embolism in a patient. Questions arise as to how to minimize these risks caused by blocking.

In some systems, the risk of intercepting blood flow to tissue fed by an artery is addressed by adding bypass or perfusion lumens such as those described in US Pat. Nos. 5,046,503 and 5,176,638.

Various exemplary systems, methods and devices are described herein for controlling blood flow in a portion of an artery or vein to control the occurrence and duration of low-flow or no-flow regions in a portion of a vessel. As a non-limiting example, the systems, devices, devices, and methods can be used to control the occurrence and duration of a dead zone region in a portion of a vessel.

In some examples, systems, methods, and devices are described for controlling (including reducing) flow obstruction during use of intravascular catheters or other similar devices. Exemplary systems, devices, and methods are described for controlling or reducing the occurrence of no-flow or low-flow regions in a vessel based on data indicative of conduction of a vascular region. Control of flow fouling can be achieved using at least one additional minimum conduction element or using a controlled shunt system. An exemplary imposed minimum conductance component can be used to impose a desired known conductance value in the vascular region. If the conductance outside the injector member is known, the fluid injection level at the injector member can be controlled so that there is an amount of fluid in a region that would normally create a no-flow or low-flow region, including a dead region. Fluid flow is used for flushing. An exemplary controlled shunt system may use sensor measurements to calculate conductance in a vascular region, thereby providing a known conductance value. That is, any of these method systems can be used to provide a known value of conduction on the exterior of the catheter member. Using these known conductance values, fluid flow can be controlled to ensure that no-flow or low-flow regions do not occur in the vessel, or that no-flow or low-flow regions occur for a duration that does not result in tissue damage or other damage.

Reducing the occurrence of flow stagnation reduces or eliminates the possibility of dead or no-flow regions forming in the vascular section.

According to some exemplary embodiments, flow fouling control may be achieved through the use of a controlled diversion system. The control shunt system includes components for measuring both proximal external conduction and distal external conduction. The measurements prevent dead flow regions in the proximal region of an injector member by modifying the flow injected at the injector member. Exemplary devices, systems, and The method can be operated passively to measure fluid flow, or can be used actively to measure fluid flow by introducing or withdrawing a volume of fluid.

The present disclosure describes devices, systems and methods that can be actively operated to prevent or reduce the occurrence of, including flushing, a dead zone that can form in a portion of the vessel proximal to a catheter during operation.

The term "applied minimum conductance element" is used herein to refer to an element that controls the reduction of flow rate in a vessel segment while ensuring that the flow rate does not fall below a certain minimum value based on an applied minimum conductance level. In this context, conduction is the inverse of resistance. In various examples, the minimum conduction level may be used to control flow to a fixed flow rate value ( herein referred to as " fixed constant") or an average flow rate value (referred to herein as a "fixed average"). For example, the time period t may be on the order of a heartbeat or a minute, and the time period T may be the time of an operation or other procedure lasting one or more hours.

According to some exemplary embodiments, flow congestion control may be achieved through the use of additional minimal conductive components and systems that are structurally designed to allow for improved flow control in extracorporeal blood return. The present invention also provides various exemplary additional minimal conductive elements that limit or prevent the formation of dead space in a region of the artery or vein proximal to such additional minimal conductive elements, and also provides specific dead space irrigation devices or subunits. system.

As used herein, an "injector member" is a device or component that includes a lumen. In one example, the lumen can be used to inject fluid into the vessel, as part of a stand-alone catheter system or as an exemplary extracorporeal circuit system for injecting blood into the vessel at a specific body location One of the components.

As used herein, the term "vascular injection point" refers to the most distal location in a vessel away from a catheter entry or vessel puncture site at which blood is injected into the body.

As used herein, the term "perimeter placed loop" refers to a Blood output (from the body to the circuit) and blood input (from the circuit to the body) catheter (or other input port and/or output port member) of an exemplary extracorporeal loop. This is a subset of all possible placements, some through peripheral loops and some through central loops.

The term "peripheral" is used herein differently than when referring to a peripheral circulatory system. For example, catheters (or other inflow port and/or outflow port components) can be placed in contact with the vena cava or lowered into the descending aorta or iliac arteries without the use of fluoroscopy. These are sometimes considered part of the central system rather than the peripheral circulatory system.

As used herein, the term "systemic perfusion system" refers to a system that is coupled to blood in the heart via an injector member that is directly coupled to a main venous feeder to the heart, such as the vena cava (inferior vena cava). or superior vena cava) or iliac vein.

As used herein, the term "local perfusion system" refers to an infuser with a device positioned such that a substantial portion (greater than about 50%) of the infused blood flow is fed to an organ system before being returned to the heart through the general circulation. A system of components.

As used herein, the term "proximal external conduction" means conduction in the space outside of the device (ie, between the device and the vessel wall) and along a region of the proximal end of the injection member tip.

As used herein, the term "distal external conduction" means total conduction from the injection site at the tip of an infusion member into the distal vessel. For an infusion member on the arterial side of the vessel, this is the conduction from the tip to the venous side of the circulation.

As used herein, the term "control shunt system" is used to measure or calculate the value of either or both proximal external conduction or distal external conduction, and then use those measurements to modify an injection Injection flow rate at the member to prevent a system of dead flow regions in the proximal region of the injector member. As used herein, such a system is controlled directly through the injector member by at least two pressure sensors and on the extracorporeal loop side of the injector member. One of displacement or flow rate control pump components. In any of the examples herein, the control shunt system can include a distributed pressure sensor array.

As used herein, the term "flow rate pattern" refers to a functional form of flow rate over a set period of time. For example, fluid flow may be set at a fluid flow rate source such that the fluid flow follows the value set by the flow rate mode. In various examples, the flow rate pattern may be a specified functional form, such as, but not limited to, a sinusoidal functional form, a sawtooth functional form, a step function functional form, or another periodic functional form in the art ( Contains more complex functional forms). In other examples where the flow rate pattern has an irregular functional form, flow rate values may be measured at regular intervals over a specified time period to provide an approximation of the irregular functional form.

In a non-limiting example herein, an additional minimal conduction component can be structurally designed to set a known specified proximal conduction around a distal region of an injection member. This proximal conduction prevents the formation of any no-flow or dead-flow regions. As another example, in a controlled shunt system according to the principles herein, the conduction that exists in the proximal exterior of an infusion member (rather than producing it) is measured and this measurement is used to control the relevant region (including any no-flow or dead-flow areas) flow rate and flushing.

In one example herein, a "bias valve" refers to a component in the wall of a catheter segment between an interior lumen and the exterior of the shaft exposed to the vessel. In one example, a "biased valve" may be structured so that if the pressure inside the lumen is greater than the pressure outside the shaft, there is a value of conduction G _forward established across the valve. In another example, a "biased valve" may be structured such that if the pressure inside the lumen is less than the pressure outside the shaft, there is a value of conduction _Gbackward established across the valve. In one example, a reasonable pressure difference between the lumen and the vessel can be expressed as G _forward >>G _backward , or G _backward is very small or close to zero.

1A shows a schematic view of an exemplary catheter system 100 including a shaft 101 of a device disposed in a portion of a vessel. Figure 1A also shows a plane 102 through an occlusion member 103 mounted on the shaft 101 and being part of the device. Shaft holding device 101 A lumen passing through the device may be included. In an exemplary catheter system 100, the occlusion assembly 103 may comprise a balloon inflated with saline or other solution. Another exemplary occlusive component 103 may include a membrane that is expanded to compress the arterial wall using force applied by a spring or other mechanical actuation. In one example, the occlusion component 103 can be configured to extend from the shaft device 101 of the catheter system 100 to contact and seal the wall of the artery or vein to substantially reduce or prevent flow. As shown in FIG. 1A , an exemplary plane 102 is perpendicular to the arterial segment. Exemplary occlusion element 103 is used to modify fluid flow across plane 102 in accordance with the principles herein. The fluid flow is relative to the flow outside the base holding the shaft. The degree of flow is driven by a pressure difference between the area in front of the occlusion element 103 (Pb) and the area behind the occlusion element 103 (Pa).

1B and 1C show exemplary graphs of fluid conduction (G ₀ ) versus time in the vascular space across the plane 102 of the occlusion component 103 . FIG. 1B shows fluid conduction (G ₀ ) versus time for a complete occlusion achieved using occlusion assembly 103 . In the example of FIG. 1B , fluid conduction decreases during the time period Δt during which the occlusion element is activated to completely occlude the vascular space. The graph of FIG. 1B shows that fluid conduction becomes zero when the occlusion element 103 is activated for full occlusion. This definition is independent of the pressure gradient/difference (F=G(Pa-Pb)). 1C is a graph depicting the condition of fluid conduction (G ₀ ) versus time during a controlled partial occlusion in which an occlusion element according to the principles herein is activated during a time period Δt . As shown in Figure 1C, the conduction does not go to zero but instead becomes one of the minimum conduction levels with a magnitude greater than zero.

A catheter can be deployed in various target locations in the vessel. However, it is extremely difficult to precisely control the diameter of the vessel at the target location. If no occlusive element is present or deployed, the leakage may be greater and may then prevent optimal control of the cis (distal region) fluid flow. This is constrained by the fact that fluid is larger in larger diameter arteries and smaller in smaller arteries. On the other hand, a complete occlusion can result in the formation of a dead zone. In accordance with the principles herein, a small controlled leakage structure can be used in conjunction with an occlusion assembly such that the dead area is flushed but leaks limited so that it does not err on the side of valuable control of distal flow by using the device. For a flow rate similar to that in the carotid or femoral arteries - 200 to 500 A downstream flow rate of ml/min would be very useful, but a flush flow rate of 20 to 50 ml/min or even less may be suitable for flushing the dead zone.

As described herein, the minimum conduction level can be a fixed constant or a fixed average. For a fixed constant, the fluid conductance _G0 remains constant over time. For a fixed average, the minimum conduction can be time-varying over a time scale t less than one of the total device start-up time. In one example, a bias valve can be structured to achieve the controlled partial occlusion such that conductance varies with a heartbeat. In this example, "fixed mean value" refers to a fluid conduction that varies in value during the time cycle of a heartbeat but has a non-zero mean value over the beat. This results in a non-zero average fluid conduction over a longer period of time.

In one example, the imposed minimum conductance is implemented as a fixed constant. An additional minimal conduction element positioned at the distal tip of an extracorporeal infusion member is structurally designed to maintain a minimum conductance that provides a fluid flow to flush out dead areas that would otherwise result from any total occlusion. The flow resistance aspect of the minimum conduction is sized such that the irrigation flow is no greater than about 50%, or preferably no greater than about 10%, of the flow the device is intended to direct through the injector member.

In one example, the imposed minimum conduction is achieved in a passive fashion. An exemplary occlusive element is structured to include an alternate fluid bypass path, allowing a bypass flow to flush dead areas that would otherwise be created by the occlusion. The flow resistance of the bypass is sized such that bypass flow is no greater than about 50%, or preferably no greater than about 10%, of the flow the device is intended to direct through the injector member.

In some examples, the occlusion component may include a soft balloon to be used for occlusion. In one example, the soft bladder may be partially inflated, resulting in some leakage conduction. This can be useful because the vessel is not uniform and the amount of leak conduction under fractional inflation is not visible to the user and/or is controllable.

FIG. 2A shows a schematic diagram of an exemplary extracorporeal circuit 200 coupled to a person. Exemplary extracorporeal circuit 200 includes a pump system 206, a heat exchanger 208, and an injector assembly 210. An exemplary extracorporeal circuit may include two connections to a patient's vessels. Such an exemplary extracorporeal circuit may be implemented to pump blood from a vessel using one connection and return blood to the vessel using another connection. An exemplary extracorporeal circuit may be used in situations where the heart is not functioning or not supplying sufficient blood flow, or may be used to modify and return blood to the systemic bloodstream or to a local area. Other modifications may include oxidation, dialysis, thermalization, removal of bacterial contaminants, removal of cancer-causing cells, and the like. 2A shows injector member 210 coupled to a vessel of a person's body at vascular infusion point 212 to return blood 214 to the body based on a flow rate modulated using pump system 206 . The most distal location in the vessel at which blood is injected into the body is referred to herein as the "vascular infusion point".

In one example, the injector member 210 may include an occlusion component to separate blood flow on one side from fluid injected through the device shaft by an integral external circuit on the other side. This can create a no-flow or restricted-flow region, ie, a dead zone, in a portion of the vessel. This dead zone can be avoided if an occlusion system is located at an exact position relative to the nearest vessel branch, but in practice this exact placement cannot be guaranteed in real patients. Therefore, a dead zone is often formed in the branch containing the injection point, where blood does not flow. If the occlusion remains in place for extended periods of time, this can potentially lead to the formation of a thrombus or blood clot. Extracorporeal blood supply circuits can be used for extended periods of time, such as but not limited to periods of time on the order of hours to days, which can be sufficient to increase the risk of thrombus or clot formation.

FIG. 2B shows an exemplary injector member 210 that is a component of the exemplary extracorporeal circuit system of FIG. 2A and returns blood to a specific location in the body vascular injection point 212 . Insufflation fluid 216 through the shaft lumen can add to the blood flow in this branch. To the extent that alternative blood flow is blocked, the infused blood can dominate the flow in the distal vessel.

FIG. 2C shows an exemplary injector member 210, which is a component of the exemplary extracorporeal circuit system of FIG. 2A and returns blood (infusion fluid 216) to a specific location in the body. The injector member 210 is coupled to an occlusion assembly 203 shown to fully occlude a portion of the vessel. As shown in FIG. 2C , in injector member 210 through occlusion device 203 in one pulse A dead zone 205 may be formed at the proximal end of the occlusion member 203 when blood is injected at the tube injection point.

3A-3B show an exemplary additional minimal conduction system according to principles herein. The externally applied minimal conduction system of FIG. 3A comprises a lumen 320 having a discrete length l , positioned along the axis of the device and beneath a component 321 such as but not limited to a soft balloon 321 such that it is relatively The flow used to flush dead areas provides a minimum conduction. Such a lumen 320, controlled by the design length and diameter, allows fluid to assume a constant flow rate and thus allows a small bypass flow. FIG. 3A shows positive fresh flush flow 324 through lumen 320 . FIG. 3B shows backflush flow 326 through lumen 320 (backflush flow). The dashed lines in FIGS. 3A-3B are used to illustrate the direction of blood flow 328 . In both Figures 3A and 3B, fluid flowing through minimal conduction can be used to flush the dead area at the proximal end of component 321, thereby preventing or minimizing unnecessary thrombus formation.

4A-4B show another exemplary additional minimal conduction system according to principles herein. FIGS. 4A-4B show an exemplary additional minimal conduction system of one or more holes or orifices 430 included in the shaft of the device just proximal to a component 421 such as, but not limited to, a balloon. An additional lumen below the additional minimal conducting element (as shown in Figures 3A-3B). In these exemplary systems, a portion of the flow 424 directed by the device toward its distal tip escapes through one or more holes (or orifices) 430 before occlusion is achieved. FIG. 4A also shows the direction of blood flow 428 . Figure 4A shows an example when the value of pressure Pb is less than pressure Pa, which results in a back flush flow (depicted as flow 424). FIG. 4B shows an exemplary plus minimal conduction system for a case where Pb is sufficiently large relative to Pa such that a forward flush flow 426 is formed.

4C shows another exemplary additional minimal conduction system according to the principles herein. The exemplary additional minimum conduction system includes an additional minimum conduction component (a spring-actuated membrane 440 ) comprising one or more holes (or apertures) 431 . One or more holes (or apertures) 431 are used to control fluid flow and provide minimal conduction. In the exemplary imposed minimum conduction system of Figure 4C, a cross-section of membrane 440 is shown. However, membrane 440 comprises a symmetrical arrangement about the device axis (similar to In an umbrella deployment) one or more substantially solid membrane portions. FIG. 4C also shows the direction of portions of blood flow 428 and fluid flow 442 leaking through one or more holes (or apertures) 431 of an additional minimal conductive element.

4D(i) and 4D(ii) show other exemplary additional minimal conduction systems according to principles herein. The exemplary system of FIG. 4D(i) includes a multi-leaf soft balloon (or other structured balloon) 450 that includes a gap that seals the vessel between the balloon leaves to provide minimal conduction. In various examples, the multi-lobed soft bladder (or other structured bladder) 450 may be formed with two, three or more bladders. Figure 4D(ii) shows cross-sectional views (through the line AA' shown in Figure 4D(i)) of different examples of a multi-lobed soft airbag (or other structured airbag) 450 . As a non-limiting example, the additional minimal conduction system may include a two-lobed soft bladder (or other two-lobed structured bladder) 455 including a gap 460 or a three-lobed soft bladder (or other three-lobed structured bladder) 465 including a gap 470 .

5A(i)-5C show other exemplary additional minimal conduction systems according to principles herein. In the exemplary system of FIG. 5A, an offset valve 550 is used to add control over the direction of flush flow to minimum conduction. Thus, directionality can produce a fixed constant flow in a direction supported by the pressure differential across the member. As an example, the pressure differential in the vessels may cause a blood pressure shift at the injection point due to each heartbeat changing sign, ie, a change from a positive pressure value to a negative value based on a systolic/diastolic pressure change. The exemplary imposed minimum conductance system can be structured such that, based on the sign (i.e., direction) of the pressure difference, irrigation flow can be "active" during only a portion of the heartbeat cycle, thereby achieving a "fixed average" minimum conductance rather than a "Fixed constant" minimum conduction.

FIG. 5A(i) shows an exemplary plus minimal conduction system including an offset valve 510 on an aperture in a catheter lumen including a component 521 such as, but not limited to, a soft balloon. The parameters P _in and P _out are the pressure inside the lumen and the pressure outside the proximal end of the soft balloon 521 . In this example, the distal region is the region where the flow rate and pressure are governed by flow through the lumen and infusion through the distal tip. In general, if _Pout is driven by the heart, the value of _Pout has a cycle similar to a heartbeat, achieving a local maximum and minimum in each cycle. FIG. 5A(ii) shows an example bias valve that may be implemented in the example system of FIG. 5A(i). Figure 5A(ii) shows an exemplary biased valve 510 mounted to a portion of a shaft of a catheter having a hole coupling the inner lumen of the shaft to the outside world and larger than the hole and anchored on at least one side A flexible plastic flap covers the hole. The exemplary bias valve is configured such that a positive pressure differential (pressure inside the shaft greater than pressure outside the shaft) causes the flexible plastic flap to open allowing fluid to flow outward, and a negative pressure differential ( The pressure inside the shaft (lower than the pressure outside the shaft) can cause the flexible plastic flap to close and seal the edge of the hole, preventing inward flow of fluid.

FIG. 5B shows an exemplary additional minimal conduction system including a bias valve 532 coupled to a component 521 . The bias valve 532 comprises a flap that is structured to open and allow fluid to flow out of but not into the central lumen of the infusion member. That is, bias valve 532 allows flow 534 when the value of pressure _Pb is lower than pressure _Pa , which occurs during certain time intervals of the heartbeat cycle. FIG. 5B shows the portion of flow 534 of the flap through biased valve 532 and the direction of blood flow 538 . In this example, only a small portion of the blood injected into the body from the extracorporeal circuit is used to flush the dead area (ie, flow 534 through the bias valve).

FIG. 5C shows an exemplary additional minimal conduction system including a flap on one end of a bypass lumen 542 that acts as a bias valve 540 . Lumen 542 has a discrete length 1 and is positioned along the axis of the injector member and below component 521, similar to that shown in FIG. 3A or FIG. 3B with an additional minimal conduction system. The coupled action of bias valve 540 and bypass lumen 542 provides a minimal conduction of convection to flush dead areas (or low flow areas). FIG. 5C shows the portion of the flow 544 of the flap through the biased valve 540 and the direction of the blood flow 548 . A flap of bias valve 540 may be mounted on the proximal or distal end of bypass lumen 542, thereby allowing the direction of irrigation flow to be selected by design. That is, if a flap structurally designed to allow only outward fluid conduction is installed at the proximal end of lumen 542 (as shown in FIG. 5C ), distally injected blood flows back to flush. If the flap is installed at the distal end of the lumen 542, the normal blood flow from the branch flushes forward and mixes with the infused blood flow at the vascular injection point. The detailed operation is determined in part by the applied pressure difference between _Pb (the pressure in front of lumen 542) and _Pa (the pressure behind lumen 542), since biased valves can be configured to only allow pressure in one direction flow up. If the values of pressures _Pa and _Pb are close enough that changes in _Pb caused by changes in systolic/diastolic pressure with the heartbeat cause the bias valve to open during certain time intervals in each heart cycle, then this exemplary implementation will be advantageous.

In accordance with the principles herein, an exemplary added minimal conduction element or an exemplary system comprising an added minimal conduction element can be used to provide selective thermal therapy. The exemplary additional minimally conductive components can be coupled to any system configured to apply a selective thermal therapy. In any exemplary implementation, additional minimally conductive components in accordance with the principles herein may be used in place of conventional blocking elements. The additional minimal conductive element may be positioned proximal to the distal tip of at least one injector member of the system for applying the selective thermal therapy. As a non-limiting example, additional minimal conductive components according to one of the principles herein may be coupled to any system in the art that applies selective thermal therapy, such as U.S. Patent No. 7,789,846 B2 or International (PCT) Application No. PCT/ The system disclosed in US2015/033529.

In any of the examples herein, the additional minimal conductive element can form an atraumatic surface, a hydrophilic coating, or a drug coating, or any combination thereof.

Figure 6A shows an exemplary controlled shunting system of the present invention. The exemplary control shunt system includes a first pressure sensor 610 and a second pressure sensor 612 . The first pressure sensor 610 may be positioned proximal to the tip of an injector member 614 of a catheter, and the second pressure sensor 612 may be spaced from the proximal end of an operator such as from the tip (or from the pressure sensing The injector member 614 is positioned on the injector member 614 at a predetermined distance (Δ) measured by the injector 610 . As non-limiting examples, the predefined spacing (Δ) may be about 2 cm, about 5 cm, about 8 cm, about 12 cm, about 15 cm, about 20 cm, about 25 cm, or about 30 cm. In various non-limiting examples, one or both of pressure sensors 610 and 612 may be implemented as silicon-based sensors (with electronic (wired) readout) embedded in the catheter wall or using An optical fiber in the lumen of the catheter provides a readout to a fiber-based pressure sensor of an appropriate computing interface system at the proximal end of the catheter. In another exemplary embodiment, one or both of the pressure sensors 610 and 612 are structured to use: a simple walled lumen with a distal opening at the location as depicted in FIG. 6A and filled with an incompressible fluid; and an external pressure sensor installed on a fluid connector at the proximal end of the catheter to measure static or low frequency pressure conducted by the fluid column of the lumen. Pressure sensor 610 may be configured to measure pressure proximal to tip (P _tip ) and pressure sensor 612 may be configured to measure pressure proximal to injector member 614 (P _b ) . FIG. 6A also shows the direction of blood flow near the catheter as a function of flow rate F _b and of injected blood flow as a function of flow rate F _tip at the tip of the injector member.

As also shown in Figure 6A, the catheter can be coupled to a flow rate source 616 of an extracorporeal system. In an exemplary embodiment, the fluid may be volume flow driven rather than pressure driven. As fluid (F _tip ) is injected into the vessel through the tip, it mixes with fluid (F _b ) from upstream and flows through downstream conduction G _tip . Upstream flow is shown in Figure 6A through conduction _Gb , as occurs in the space between the artery (or vein) wall and the catheter. It may be difficult to directly measure or predict the value of one of the conduction _Gb . Even where pressure sensors 610 and 612 are positioned to measure _{Pb and Ptip ,} it may still be difficult to measure _Fb directly if _Gb is unknown. Exemplary systems and methods in accordance with the principles herein can be used to determine a value of _Gb .

In one example, the flow rate source can be used to control a volumetric flow rate. The exemplary flow rate source can be, but is not limited to, a displacement pump, a syringe pump, or a rotary pump.

In one example, the flow rate source can be used to control the flow rate such that fluid injected at the distal tip follows a series of volumetric impulses. In this example, the series of volumetric impulses can be modeled according to a step function. The flow rate source may be a pump executing instructions from a processing unit of a console to deliver each of the series of pulses, or a step function initiated and continuously delivered based on a first signal from the console Pulse until a second signal from the console causes the pump to stop operating a pump.

In other examples, the flow rate source can be used to control the flow rate such that the fluid flows according to other A type of functional form such as, but not limited to, a sine, sawtooth, or other circular function form flows.

In any of the examples herein, the flow rate source can be used to control the flow rate to establish a flow rate pattern. As mentioned above, the flow rate pattern may be based on an arbitrary waveform or other type of function such as, but not limited to, a sine function, sawtooth function or other circular function.

In one non-limiting example according to the principles of FIG. 6A , an injector member is coupled to two pressure sensors, wherein the injector member is driven by an external flow rate control member to allow measurement or calculation of the proximal external conductance and the value of distal external conduction. An exemplary system enables inference of flow around an injector member of a catheter from data indicative of pressure measurements.

A control shunt system is provided for judging two conductions, including the system depicted in FIG. 6A. The first conduction, referred to as the proximal conduction (G _b ), is the conduction in the extracatheter vascular space between the planes defined by the two pressure sensors 610 and 612 . The second conduction, called distal conduction (G _tip ), is the conduction from the tip to the blood returning to the core system (or ground in a flow sense). In the absence of measurements, these two conductions generally cannot be inferred, since the calculations will use data indicative of the size and shape of regional vessels. In the case of G _tip , the calculation will use data indicative of the state and/or extent of damage of the vascular bed. Knowledge of the values of these two conductances can provide clinical benefit because they represent one measure of the local state of vasodilation/vasoconstriction in the patient. Using pressure sensors 610 and 612 to measure P _b and P _tip , if the conduction between them is controlled conduction as previously described plus one of the minimum conduction, then the flow F _b =G _b (P _b -P _tip ) to estimate the flow. In an exemplary embodiment where the calculation of _Gb includes data indicative of the surface of the vein or artery, _Gb cannot be determined a priori. In general, _Gtip cannot be determined prior to an operation involving injection member placement or other medical procedure.

Exemplary systems and methods for calculating both _Gb and _Gtip in vivo for a patient during a procedure or other medical procedure are provided herein. Using a linear approximation, the flow balance around the distal tip of the injection member can be expressed using two equations, as follows: (1)....F _b =G _b (P _b -P _tip )

(2)....(F _b +F _tip )=G _tip (P _tip ) The value of F _tip can be set from a pump such as but not limited to flow rate source 616 . The exemplary system of FIG. 6A can be used to measure the values of pressure _{Pb and pressure Ptip .} Using these values, the equation can be reduced to: (3)....G _tip =F _tip /P _tip +Gb(P _b -P _tip )/P _tip where G _tip and G _b are unknowns. During an operation using the infusion member to return blood to the body or other medical procedure, the initial infusion flow at time _T0 may be used as _F'tip (as a non-limiting example, approximately 250ml/min). At time T ₁ , the flow value can be changed to F" _tip (as a non-limiting example, about 275 ml/min, a 10% increase). These non-limiting examples of flow at times T ₀ and T ₁ Values can be chosen to fall within a desired clinical range for a particular bone at the point of injection and for a particular clinical application. The exemplary system of Figure 6A can be used to measure the values of pressure _{Pb and pressure Ptip at} time point _T0 (P' _b and P' _tip ) and the values _of pressure P _b and pressure P _tip at time point T1 (P" _b and P" _tip ). Using four different pressure values and two Different injection flow values, i.e. introducing F' _tip , P' _tip , P' _b at time T ₀ and introducing F" _tip , P" _tip and P" _b at time T ₁ , yield two (2) equations, each The equation has two (2) unknowns. These equations can be used to calculate the values of G _b and G _tip . It is readily apparent to those of ordinary skill that equations (1), (2) and (3) are non-limiting examples of equations for flow, conduction and pressure in a vascular region. Other equations, including more complex versions of the equations, may be applicable. For example, equations where conductance is not independent of pressure but is itself a function of pressure can also be handled by using repeated pressure measurements at different values of the applied flow F _tip to build more equations and allowing the pair to be linear Or even solve in the form of conduction (G) of quadratic or higher order pressure functions.

As described herein, the flow rate source can be used to control the flow rate such that the injected fluid at the distal tip follows a step function or other type of function such as, but not limited to, a sinusoidal, sawtooth or other circular function. form) flows. in other instances In , the flow rate can be modeled based on measurements of a response function of fluid flow and solved for an appropriate functional form.

Provided herein are exemplary systems and methods for calculating both _Gb and _Gtip in vivo for a patient during a lengthy operation or other medical procedure. As a non-limiting example, such a lengthy operation (or other medical procedure) can last on the order of hours or days. An exemplary method may include applying a stepwise change (ie, a discrete value change from a baseline) to F _tip for a short time interval ( t ₁ ) in a regularly repeated cycle during an operation or other medical procedure. As a non-limiting time, the step change may be applied to _Ftip within 5 minutes before each hour of an operation or other medical procedure (ie, ti ₌ 5 minutes). At the end _of time interval t1 , the value of F _tip returns to the baseline value. This exemplary method for modifying the value of _Ftip can be used to measure _Gb and _Gtip per hour during lengthy operations or other medical procedures using the methods described herein. These exemplary systems and methods have clinical application in monitoring vascular status (vasodilation/vasoconstriction) or in detecting the progress of thrombus formation or the timing of thrombus lysis.

Another exemplary clinical application of the exemplary systems and methods follows. Using the values calculated for _Gb and _Gtip during an operation or other medical procedure, the amount of flow _Fb flushing the space proximal to the _tip can be determined from the measured pressures Pb and _Ptip . If the flow F _b falls outside a desired range of values, F _tip can be adjusted to adjust F _b .

Another clinical application of the systems and methods is the determination of the heat capacity of blood applied to tissue. During an operation or other medical procedure, _{Fb and Ftip can} mix in the region at the distal end of the tip. If the blood flow _{Fb is at a first temperature and the injected blood flow Ftip is} at a second temperature different from the first temperature, the heat capacity of the blood applied to the tissue in the distal region can be directly calculated and can be used Adjustment of the temperature of the injected blood compensates for warm or cold blood flow F _b . Alternatively, the procedure of controlled rewarming can be accomplished by adjusting the flow ratio _{Fb:Ftip and} its equal temperature difference. An exemplary method for measuring _Gb and _Gtip described herein may be applied one or more times during a procedure or other medical procedure. This method can be generalized to use more than one stepwise variation of F _tip , in which case the operator can measure the values of _Gb and G _tip to determine how they might vary outside the linear approximation of equations (1 to 3) . An operator can implement an exemplary method in accordance with the principles herein by, for example, setting _Ftip directly; recording sensor records; and performing calculations using a computing device. In another exemplary embodiment, a computing device or system herein may include at least one processing unit programmed to execute processor-executable instructions to cause a controller of an exemplary system Measurement routines for measuring the values of _Gb and _Gtip as described herein are automatically implemented. The exemplary system can be structured to allow a user to set a nominal value for F _tip and execute processor-executable instructions to set the F tip at desired intervals, such as but not limited to every 30 or 45 or 60 minutes or other time intervals. ) to perform automatic measurement of one of G _b and G _tip . In any example herein, the computing device can be a console.

6B shows an exemplary control shunt system according to one of the principles herein. The exemplary system includes two pressure sensors used in conjunction with a concentric cylindrical two-port catheter to support an independent local extracorporeal circuit. As shown in Figure 6B, two pressure sensors 610' and 612' are coupled to an insertion member 614, one of the components of an extracorporeal loop access catheter of the concentric shaft type. In this example, the outer shaft 618 supplies blood to the extracorporeal circuit 618 and the inner shaft 614 acts as an insertion member for returning blood to a location in the body. Figure 6B also shows the dashed line 615 of blood flow outflow to the extracorporeal loop and the dashed line 617 of blood flow around a catheter (Fb). As non-limiting examples, US 7,704,220 and US Patent No. 7,789,846 disclose examples of concentric extracorporeal access catheters that may be implemented in one or more of the exemplary systems according to the principles herein.

6C and 6D show exemplary systems that may be used to calculate values for conduction in a region of the vessel proximal to the heart, according to the principles herein. In the example of FIGS. 6C and 6D , the exemplary system is shown positioned in a region of the aortic arch. As shown in FIG. 6C , the exemplary system includes pressure sensors 610 and 612 coupled to a catheter member 620 . In this example, pressure sensor measurements can be used to calculate conductance as described herein. In one example, using pressure measurements, conductance can be calculated according to the exemplary methods described above for calculating both _Gb and _Gtip in vivo. In the example of FIG. 6C , fluid flow may be introduced from a distal tip of catheter member 620 . FIG. 6D shows another exemplary system that is similar to FIG. 6C , but catheter 620 includes a proximal port 622 that allows fluid flow from a more central region of catheter member 622 .

In any of the exemplary systems, methods, devices and devices herein, the fluid injected through the injector member may mix with the fluid passing through the catheter or the external space surrounding the device (external fluid). If the fluid streams mix, they form a mixed fluid (herein also referred to as a mixed distal stream) in a region distal to the injection point. If a known concentration (in mg/ml or other mass/volume unit) of a drug or agent is added to the infused fluid, the concentration of the drug or agent in the distal mixed fluid is unknown, Unless the ratio of the external fluid flow rate and the injected fluid flow rate is known. Exemplary systems described herein can be used to set external conductance (plus minimal conduction components) or to quantify external conductance (control shunt system). Based on the conduction data, the external fluid flow rate can be measured or calculated. Using the calculated value of the external fluid flow rate and the infused flow rate set by the pump system (or other system) coupled to the injector member, the concentration of the drug or medicament added to the infused fluid can be adjusted to achieve the desired rate in the distal fluid. The desired drug concentration is achieved in the mixture.

In any instance herein, a drug or agent can be any substance used to diagnose, cure, treat or prevent a disease. For example, the drug or agent may comprise an electrolyte solution, nanoparticles, biologics, small molecules, macromolecules, polymeric materials, biopharmaceuticals, or any other drug or agent that can be used in the bloodstream.

An exemplary system in accordance with the principles herein can be used to provide at least two regions of selective thermal treatment. This exemplary system includes an integral outer loop. The exemplary extracorporeal circuit includes an injector member comprising a distal tip disposed at a vascular location and an additional minimal conductive element disposed proximal to the distal tip. The exemplary system may also include: a first port for withdrawing blood from the body; a second port for returning blood to the body; a first pump positioned between the first port and the second port between the two ports to draw blood from the first port pumps to the second port; a branch section positioned between the first pump and the second port; a third port coupled to the branch section positioned at the injection and a second pump positioned between the branch section and the third port. The second pump can be configured to control a flow rate through the third port into the injector member outside the branching section. The exemplary system can also include a first heat exchanger disposed between the first port and the second port and a second heat exchanger disposed between the second pump and the injector member. The first heat exchanger may be structured to set a temperature of blood injected into the second port to a first temperature level. The second heat exchanger may be structured to set the temperature of blood injected into the injector member to a second temperature level different from the first temperature level. The first heat exchanger may be disposed between the branch section and the first port or between the branch section and the second port.

Exemplary systems for providing at least two regions of selective thermal therapy can include an occlusive element or an additional minimally conductive element disposed proximal to the distal tip of the injector member.

Another exemplary system for providing at least two regions of selective thermal therapy according to the principles herein may comprise an extracorporeal circuit comprising a An injector component. The exemplary system can further include a control shunt system at a proximal end of the distal tip. The control shunt system may comprise: a first sensor for measuring flow proximal to a distal tip of at least one injector member; and a second pressure sensor for measuring A second pressure sensor positioned at a distance greater than or approximately equal to twice a diameter of the vessel from the proximal end of the distal tip. In other examples, the spacing may be greater than or approximately equal to three, five, or ten times the diameter of the vessel. In another example, the distance from the proximal end of the distal tip is greater than about 1.0 cm. The exemplary system may also include: a first port for withdrawing blood from the body; a second port for returning blood to the body; a first pump positioned between the first port and the second port between two ports to pump blood from the first port to the second port; a branch section positioned between the first pump and the second port; a third port coupled to the branch section, the third port positioned on a body exterior of the injector member; and a first A second pump is positioned between the branch section and the third port. The second pump can be configured to control a flow rate through the third port into the injector member outside the branch section. The exemplary system can also include a first heat exchanger disposed between the first port and the second port and a second heat exchanger disposed between the second pump and the injector member. The first heat exchanger may be structured to set a temperature of blood injected into the second port to a first temperature level. The second heat exchanger may be structured to set the temperature of blood injected into the injector member to a second temperature level different from the first temperature level. The first heat exchanger may be disposed between the branch section and the first port or between the branch section and the second port.

Exemplary systems for providing at least two regions of selective thermal therapy can include an occlusive element or an additional minimally conductive element disposed proximal to the distal tip of the injector member.

7A shows a schematic diagram of an exemplary three-port extracorporeal loop for providing one of at least two regions of selective thermal therapy, according to the principles herein. As a non-limiting example, the extracorporeal circuit can be implemented to control blood flow to the core and attached local branches under independent flow rate and temperature control. In the non-limiting example of FIG. 7A , the extracorporeal system 700 is a three-port, two-region extracorporeal circuit in which an aortic venous-arterial (VA) extracorporeal circuit 710 draws blood from the body via a first port 711 and uses a Pump 712 and oxygenator/heat exchanger 714 to return blood via a second port 715 . The exemplary system may include a displacement or volume driven pump 716 positioned on a branch 718 of the primary circuit and pulling a controlled volume flow rate of blood out of the primary circuit and through a The independent heat exchanger 720 , a third port 721 and the distal injector member 722 inject blood into a region 724 of the body. In a non-limiting example, branch 718 may be a locally perfused hypothermic branch. The non-limiting exemplary system of FIG. 7A allows for the establishment of two independent controls in the body when deployed with appropriate zone temperature sensors. temperature zone. In other examples, branch 718 may be coupled to the primary circuit either before or after primary circuit oxygenator 714, depending on whether the user desires to oxygenate injector member blood. In these instances, if the system is used to apply a localized low temperature through the distal injector member, such as disclosed in International (PCT) Application No. PCT/US2015/033529, a concentric cylinder on the injector member flows out The lack of can lead to an increase in the conduction cooling of the component catheter to the artery in which the component catheter is placed. This effect may require some additional warming on the main loop circuit to achieve an equivalent thermal target in the area of the body that needs to be controlled.

7B shows another exemplary extracorporeal circuit for providing at least two regions of selective thermal therapy according to the principles herein. Similar to FIG. 7A, the extracorporeal system 700' of FIG. 7B includes a main VA extracorporeal circuit 710 that draws blood from the body via a first port 711 and uses a pump 712, an oxygenator 713, and a heat pump 712. The exchanger 714 returns the blood via a second port 715 . In a non-limiting example, oxygenator 713 and heat exchanger 714 may be a combined unit. The exemplary system 700' also includes a displacement or volume driven pump 716 positioned on a branch 718 to pull a controlled volume flow rate of blood out of the main loop and through an independent The heat exchanger 720, a third port 721 and a distal injector member 722 inject blood into a localized area of the body. In the example of extracorporeal system 700', the injector member may also include: an occlusive member; an additional minimal conductive member (according to any of the examples herein, including any of FIGS. 3A-5C ); or a pressure sensor pair coupled to the injector member (according to any of the examples herein, including FIG. 6A or FIG. 6B ); or a pressure sensor pair and an occlusion member or an additional minimal conductive component both. In the non-limiting exemplary system of FIG. 7B , injector member 722 includes both an additional minimal conductive element 726 and a coupled pressure sensor pair 728 . In the example of Figure 7B, the oxygenator 714 on the primary circuit is positioned in front of the regional injector branch 718 and thus the locally injected blood flow is oxygenated.

FIG. 7C shows another exemplary extracorporeal circuit for providing at least two regions of selective thermal therapy according to the principles herein, comprising components similar to those described in connection with FIG. 7B components. However, in the extracorporeal system 700" of Figure 7C, the oxygenator 713 on the primary circuit is positioned along the circuit behind the local injector branch, and thus locally infused blood is not directly oxygenated. In one non-limiting example, The oxygenator 713 and the heat exchanger 714 may be a combined unit.

The non-limiting exemplary system of any of FIGS. 7A-7C may include a temperature sensor coupled to a region of the body to allow providing temperature measurements at two independently controlled temperature regions in the body. For example, at least one temperature sensor may be positioned at or otherwise coupled to the region infused by the second port, and at least one temperature sensor may be positioned at the localized region of the body infused by the distal injector member or otherwise coupled to the local area. At least one temperature sensor disposed at or otherwise coupled to the region perfused by the second port may be configured to measure an average core body temperature and/or an average system temperature of a portion of the body. At least one temperature sensor disposed at or otherwise coupled to the local area of the body infused by the distal injector member is configured to measure the temperature of the local area.

The non-limiting exemplary system of any of FIGS. 7A-7C can include a temperature sensor coupled to at least one of the heat exchangers.

Other non-limiting exemplary systems according to the principles of FIGS. 7A-7C may be structured to perform other procedures on blood in an extracorporeal circuit, such as but not limited to dialysis, oxidation, purification, pharmacological manipulation, photolysis or may be used for blood other programs. Any one or more of these procedures may be performed on the main loop or branch or both (with different amounts or numbers of one or more of these procedures performed on the loop or branch).

In the non-limiting illustrative example of FIGS. 7A-7C , the primary loop is depicted as a VA loop. However, in other exemplary embodiments, the primary circuit may be a venous-venous (VV) circuit rather than a VA circuit. In an exemplary VV circuit, blood is drawn from the venous side of the vessel (usually from the iliac vein or inferior vena cava) and returned into the vena cava, usually above or close to the heart. In another example, VV can be performed using a single puncture in the femoral vein, and A single dual lumen catheter can be used to place the VV circuit blood out and return using one lumen of the catheter each.

An exemplary system in accordance with the principles herein may include one or more consoles. Exemplary consoles can include one or more user interfaces structured to receive pumps, heat exchangers, and/or oxygenators representing the main circuit and/or local branches of the exemplary extracorporeal system The input to be set for one or more devices. An exemplary console may include one or more processing units for executing processor-executable instructions to cause one or more of the pump, heat exchanger, and/or oxygenator to Change to a different operating setting and/or maintain a specific operating setting. In any instance, the input may be received at the one or more user interfaces directly from a user or from another computing device. An exemplary console may include at least one memory for storing processor-executable instructions that may be implemented using the one or more processing units. An exemplary console can be configured to store and/or transmit data indicative of system settings and/or any measurement data derived based on execution of one or more programs using the exemplary system coupled to the console.

8A shows an exemplary extracorporeal loop system 800 coupled to a console 802 according to the principles herein. Similar to FIG. 7B , the exemplary extracorporeal circuit system 800 of FIG. 8A includes a main VA extracorporeal circuit 810 that draws blood from the body via a first port 811 and uses a pump 812 , an oxygenator 813 And a heat exchanger 814 returns the blood via a second port 815 . In a non-limiting example, oxygenator 813 and heat exchanger 814 may be a combined unit. The exemplary extracorporeal circuit system 800 also includes a displacement or volume driven pump 816 positioned on a branch 818 to pull a controlled volume flow rate of blood out of the main circuit and through a The independent heat exchanger 820, a third port 821 and a distal injector member 822 inject blood into a localized area of the body. Also similar to the non-limiting exemplary system of FIG. 7B , the injector member includes an additional minimum conduction element 826 and a pressure sensor pair 828 . In the example of FIG. 8A , the console 802 is coupled to a row located on a branch 818 Volume or volume drives pump 816 and pressure sensor pair 828. In other examples, console 802 can be coupled to various components of the system, including any one or more of the pumps, heat exchangers, and/or oxygenators of the exemplary system.

The non-limiting exemplary system of FIG. 8A may include temperature sensors coupled to regions of the body to allow providing temperature measurements at two independently controlled temperature regions in the body. For example, at least one temperature sensor may be positioned at or otherwise coupled to the localized region of the region infused by the second port, and at least one temperature sensor may be positioned at the localized portion of the body infused by the distal injector member area or otherwise coupled to the local area. At least one temperature sensor disposed at or otherwise coupled to the region perfused by the second port may be configured to measure an average core body temperature and/or an average system temperature of a portion of the body. At least one temperature sensor disposed at or otherwise coupled to a localized region of the body infused by the distal injector member may be structured to measure the temperature of the localized region.

In one example, the console 802 can be structurally designed as an operation console. In this example, the operating console may include a water cooler/heater for driving a heat exchanger and a graphical user interface structured to display user instructions for carrying out the operational steps of an operational sequence . The graphical user interface of the console 802 can be structured to implement the sequence of operations to cause the extracorporeal loop to control the temperature of the blood perfused by the second port to adjust a temperature measurement reported by the at least one temperature sensor to maintain at within a core body target range and causes the extracorporeal loop to control the temperature of blood infused into the localized region such that at least one temperature sensor reports a temperature measurement within a target region temperature range.

Exemplary console 802 can be configured to automate the performance of Gb and Gtip measurements using the methods described herein for controlling a shunt system. Based on the received input, the console can cause a processor to execute instructions for recording data indicative of the value of the flow in the injector member and the pressure on the injector member, while also controlling the amount of the injected flow rate, Automated performance of a method for assisting or enabling measurement of proximal conduction and distal conduction at the injector member on principles according to any one of the examples described herein. Such an exemplary console 802 can Architected to automate the controlled shunt system applied to injectors coupled to an extracorporeal circuit or another catheter system having an extracorporeal volumetric flow rate source such as but not limited to the example in FIG. 6A member.

8B shows another exemplary system 850 coupled to a console 852 according to the principles herein. Exemplary system 850 includes a flow rate control source 860 and a reservoir 862 . As a non-limiting example, an exemplary flow control source 860 and reservoir 862 may be, but is not limited to, a syringe or syringe driver. Exemplary system 850 also includes a distal injector member 872 coupled to a localized region of the body. Injector member 872 includes an additional minimum conductive element 876 and a pressure sensor pair 878 . In the example of FIG. 8B , console 802 is coupled to flow rate control source 860 and pressure sensor pair 878 . In the example of FIG. 8B , flow rate control source 860 and reservoir 862 are used to establish two Ftip settings (according to any of the examples described above) that control the split system. As a non-limiting example, a setting based on instructions received at the console may first draw blood to the reservoir at, say, 50ml/min for 2 minutes, then wait for two minutes, then return blood at 50ml/min for two minutes. In this non-limiting example, this establishes Ftip=-50ml/min, Ftip=0 and Ftip=+50ml/min. Based on input received at console 852, eg, from a user or other computing device, instructions may be executed to execute any other desired procedures according to the settings specified in the input.

An exemplary system in accordance with the principles herein can include one or more controllers for controlling a fluid flow. For example, the one or more controllers may be coupled to an infusion member to control fluid flow out of the distal tip of the injector member.

An exemplary system in accordance with the principles herein can include a console. FIG. 9 shows an exemplary console 905 including at least one processing unit 907 and a memory 909 . An exemplary console can include, for example, a desktop computer, a laptop computer, a tablet computer, a smartphone, a server, a computing cloud, combinations thereof, or any combination thereof according to the principles herein. Any other suitable device for electronic communication of a controller or other system. Exemplary processing unit 907 may include, but is not limited to, a microchip, a processor, a processor, a special purpose processor, an application specific integrated circuit, a microcontroller, a field programmable gate array, any other suitable processor, or a combination thereof. Exemplary memory 909 may include, but is not limited to, hard memory, non-transitory tangible media, storage disks, optical disks, flash drives, computing device memory, random access memory (such as but not limited to DRAM, SRAM , EDO RAM), any other type of memory, or a combination thereof.

In one example, the console may include a display unit 911 . Exemplary display units 911 may include, but are not limited to, an LED monitor, an LCD monitor, a television, a CRT monitor, a touch screen, a computer monitor, a touch screen monitor, a mobile device ( such as but not limited to a screen or display of a smartphone, a tablet computer or an e-book), and/or any other display unit.

10A-10B show example methods that may be implemented using an example shunt system or an example system comprising at least two pressure sensors coupled to a catheter member, according to principles herein. One or more of the steps of FIGS. 10A-10B may be performed using a controller based on a command or other signal from a processing unit executing instructions stored to a memory.

10A shows an exemplary method comprising the steps of: (step 1002) controlling the flow of fluid injected at the distal tip of the injector member to a predetermined flow rate pattern during a time interval T ; (step 1004) recording pressure measurements using the first pressure sensor and the second pressure sensor for a time interval T; and (step 1006) calculating a flow rate at the distal tip using data indicative of the pressure measurements and the predetermined flow rate pattern At least one of a proximal external conduction or a distal external conduction. The distal tip may be part of an injector member or a catheter member of the external circuit. In one example, the flow rate pattern can be controlled using an injection flow rate source. In one example, the injection flow rate source can be a pump.

10B shows another example method that may be implemented using an example shunt system or an example system comprising at least two pressure sensors coupled to a catheter member, according to principles herein. In step 1052, blood flow to be injected at the distal tip of an injector member (or a catheter member) is controlled to a first constant flow rate for a first time interval (T _A ). In step 1054, at least one first pressure measurement (P _1A and P _1B ) is recorded during the first time interval (T _A ) using each of the first pressure sensor and the second pressure sensor. In step 1056, blood flow to be injected at the distal tip of the injector member is controlled to a second constant flow rate different from the first constant flow rate for a second time interval (T _B ). In step 1058, at least one second pressure measurement (P _2A and P _2B ) is recorded during the second time interval (T _B ) using each of the first pressure sensor and the second pressure sensor. In step 1060, at least one processor of the processing unit is used to calculate the injector using data indicative of the first pressure measurement, the second pressure measurement, the first constant flow rate, and the second constant flow rate At least one of a proximal external conduction or a distal external conduction at the distal tip of the member (or catheter member).

In one example, the exemplary console can cause the display unit to display an indication of either the proximal external conduction or the distal external conduction or both based on the calculation.

In one example, the processing unit may also be _caused to calculate _{a proximal} external conduction or a A projection of at least one of the distal external conductions.

11 is a block diagram of an illustrative computing device 1110 that may be used to perform an operation according to the principles herein. In any of the examples herein, the computing device 1110 can be structured as a console. FIG. 11 is also referred to again for clarity and provides greater detail regarding the various elements of the exemplary system of FIG. 9 . Computing device 1110 may include one or more non-transitory computer-readable media for storing one or more computer-executable instructions or software to implement the examples. The non-transitory computer readable medium may include, but is not limited to, one or more of the following types of hard memory, non-transitory tangible media (e.g., one or more storage disks, one or more optical disks, one or more flash drive), etc. For example, memory 909 included in computing device 1110 may store computer readable and computer executable instructions or software for performing the operations disclosed herein. For example, memory 909 may store A software application 1140 for one of the disclosed operations (eg, causing a controller control flow, recording a pressure sensor measurement, or performing a calculation). Computing device 1110 may also include architectable and/or programmable processor 907 and an associated core 1114, and optionally for executing computer-readable and computer-executable instructions or software stored in memory 909 and user One or more additional configurable and/or programmable processing devices, such as processor 1112' and associated core 1114' (e.g., in the case of computing devices). Processor 907 and processor 1112' may each be a single-core processor or a multi-core (1114 and 1114') processor.

Virtualization can be used in the computing device 1110 to allow dynamic pooling of infrastructure and resources in the console. A virtual machine 1124 may be provided to handle a program running on multiple processors such that the program appears to use only one computing resource rather than multiple computing resources. Multiple virtual machines can also be used with one processor.

Memory 909 may include a computing device memory or random access memory, such as DRAM, SRAM, EDO RAM, and the like. Memory 909 may also include other types of memory or combinations thereof.

A user may interact with computing device 1110 through a visual display unit 1128 , such as a computer monitor that may display one or more user interfaces 1130 that may be provided in accordance with example systems and methods. Computing device 1110 may include other I/O devices for receiving input from a user, eg, a keyboard or any suitable multi-touch interface 1118, a pointing device 1120 (eg, a mouse). Keyboard 1118 and pointing device 1120 may be coupled to visual display unit 1128 . Computing device 1110 may include other suitable conventional I/O peripherals.

Computing device 1110 may also include one or more storage devices 1134, such as a hard drive, CD-ROM, or other computer-readable device for storing data and computer-readable instructions and/or software for performing the operations disclosed herein media. Exemplary storage device 1134 may also store one or more databases for storing any suitable information desired to implement the exemplary systems and methods. The database can be manually or automatically updated at any suitable time to add, delete and/or update resources One or more items in the library.

Computing device 1110 may include devices architected to communicate via one or more network devices 1132 over a variety of connections, including but not limited to standard telephone lines, local area network (LAN), or wide area network (WAN) links (e.g., 802.11, T1 , T3, 56kb, X.25), broadband connections (eg, ISDN, frame repeaters, ATM), wireless connections, Controller Area Network (CAN), or some combination of any or all of the above ) interfaces with one or more networks (eg, LAN, WAN, or the Internet). Network interface 1122 may include a built-in network adapter, network interface card, PCMCIA network card, cardbus network adapter, wireless network adapter, USB network adapter, modem, or other device suitable for interfacing computing device 1110 Any other device connected to any type of network capable of communicating and performing the operations described herein. Additionally, computing device 1110 may be any computing device, such as a workstation, desktop computer, server, laptop computer, handheld computer, tablet computer, or computer capable of communicating and capable of performing the operations described herein. Other forms of computing or telecommunications devices with sufficient processor power and memory capacity.

The computing device 1110 can run any operating system 1126, such as any version of the Microsoft® Windows® operating system, various versions of the Unix and Linux operating systems, any version of MacOS® for Macintosh computers, any embedded operating system, any real-time operating system system, any open source operating system, any proprietary operating system, or any other operating system capable of running on a console and performing the operations described herein. In some examples, the operating system 1126 can run in a native mode or an emulated mode. In one example, the operating system 1126 can run on one or more cloud machine instances.

In non-limiting examples, a computing device according to the principles herein may comprise any one or more of the following: a smartphone (such as but not limited to an iPhone®, an Android ^™ phone, or a Blackberry®), a Tablet computer, a laptop computer, a tablet touch computer, an electronic game system (such as but not limited to an XBOX®, a Playstation® or a Wii®), an e-reader (e-reader) and/or other E-readers or handheld computing devices.

In any of the examples herein, a computer program can be used to implement at least one method herein. The computer program (also known as a program, software, software application, script, application, or code) may be written in any form of programming language (including compiled or Deployment in any form (including as a stand-alone program or as a module, component, subroutine, object, or other unit suitable for use in a computing environment). A computer program may, but need not, correspond to a file in a file system. A program can be stored in a single file dedicated to the program in question or in multiple coordinated files (for example, a file that stores one or more modules, subprograms, or code sections) that hold other programs or data (for example, in One or more scripts in a markup language file) in a part of a file. A computer program can be deployed to be executed on one computer at one site or on multiple computers distributed across multiple sites and interconnected by a communication network.

An exemplary computing device may include an application ("App") for performing functions such as analyzing temperature sensor data, pressure sensor data, and computing conduction, as described herein. As a non-limiting example, the App may be structured to download as an *.apk file for an Android ^™ compatible system or an *.app file for an iOS® compatible system.

An exemplary console in accordance with the principles herein may implement a control program for a sequence of operations such as that described in International (PCT) Application No. PCT/US2015/033529, which is incorporated herein by reference. For example, the console may include a display including a user interface and cooler/heater for driving the heat exchanger. The exemplary console can be coupled to: at least one first temperature sensor positioned to measure an average core body temperature and/or an average system temperature of a portion of the body perfused using the second port; and at least one second A temperature sensor positioned to measure the temperature of a localized region infused by the injector member. The user interface is structured to display user instructions for performing the operational steps of an operational sequence. A non-limiting exemplary console can include as defined herein A user interface and computing means for implementing a semi-automatic control program so that during all phases of an operation temperature bands can be set in the device and if during each phase the sensor temperature deviates from the target range, the operator can be notified to adjust the cooler temperature. A non-limiting exemplary console may include a user interface and computing device as defined herein for implementing a fully automated control program such that during all phases of an operation, the Temperature bands are set in the device and the system can be structured to automatically adjust the cooler temperature if the sensor temperature deviates from the target range during each phase.

Any of the exemplary systems and methods herein may be used to establish and control two distinct temperature zones of at least part of a body for at least part of a therapeutic procedure in a patient suffering from a local or global traumatic ischemic or circulatory injury , such as described in International (PCT) Application No. PCT/US2015/033529. An exemplary method may include coupling a systemic perfusion extracorporeal circuit (SPEC) to the body using a peripherally placed circuit and coupling a partial perfusion extracorporeal circuit (LPEC) to intravascular flow to a local target region of the body ( blood such as but not limited to the brain). The SPEC may include a SPEC input port and a SPEC output port in contact with blood flowing within the vessel, a SPEC pump, and a SPEC heat exchanger. The LPEC may include an LPEC input port and an LPEC output port in contact with blood flowing within the vessel, a LPEC pump, and a LPEC heat exchanger. The LPEC input port is positioned to perfuse a localized target area of the body. The method comprises: positioning at least one SPEC sensor to measure mean core body temperature and/or mean systemic temperature of a body perfused by the SPEC; positioning at least one LPEC sensor to measure a localized target area perfused by the LPEC temperature; performing at least one minimum operating sequence of operating steps; and implementing a control program to record measurements of the at least one LPEC sensor and the at least one SPEC sensor and independently control blood flow of the SPEC and the LPEC, respectively flow rate and a heat exchanger temperature. The LPEC may comprise an injector member comprising a distal tip positioned to contact blood flowing within the vessel, wherein the LPEC injector member is positioned to perfuse the body local target area. The LPEC may include an additional minimum conduction element or a controlled shunt system or both according to the principles described herein. In an example where the LPEC includes a controlled split system, the LPEC pump can be used as a source of injection flow rate for the controlled split system.

The LPEC input port can be placed in contact with an artery downstream of the left common carotid artery, the right common carotid artery, or one of these locations.

In one example, the control routine may cause the SPEC to control the temperature of blood flow injected by the SPEC to adjust the temperature measurements reported by the SPEC temperature sensor to remain within a target core body temperature range, and cause the LPEC to control The temperature of the blood injected into the target zone causes one or more LPEC temperature sensors to report a temperature measurement according to a specified pattern of target zone temperature values. The SPEC temperature sensor can be one or more of a bladder temperature sensor or a rectal temperature sensor.

In another example, the control program may cause the SPEC to adjust the body's body temperature such that one or more SPEC temperature sensors indicate an average temperature in the range from about 32°C to below about 37°C, and cause the SPEC The LPEC controls the temperature of the blood to the target zone such that one or more LPEC temperature sensors indicate a temperature below about 30°C. The control program may cause the SPEC to increase blood temperature to prevent the average temperature from dropping below about 32°C. The control program may cause the LPEC to cool the blood temperature to a value in the range of about 10°C to about 30°C.

Any of the exemplary systems herein may include a control system programmed to execute the control program. For example, the control system can be programmed to set a flow rate and a temperature at the LPEC pump and LPEC heat exchanger independently of the flow rate at the SPEC pump. The control system can be programmed to cause the LPEC to control the temperature of blood flow to the target zone automatically or based on a manual input. The control system can be programmed to cause the SPEC to increase blood temperature to prevent the average temperature from dropping below about 32°C. The control system can be programmed to cause the LPEC to cool the blood temperature to a value in the range of about 10°C to about 30°C.

in conclusion

Although various inventive embodiments have been described and illustrated herein, those of ordinary skill will readily conceive of one of the inventions for performing the functions described herein and/or obtaining the results described herein and/or the advantages described herein. Various other components and/or structures of one or more, and each of such variations and/or modifications should be considered within the scope of the embodiments of the invention described herein. More generally, those of ordinary skill will readily understand that all parameters, dimensions, materials, and structural designs described herein are meant to be exemplary and actual parameters, dimensions, materials, and/or structural designs will depend upon use of the teachings of the present invention. specific application. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. Therefore, it should be understood that the foregoing embodiments are presented by way of example only and that within the scope of the appended claims and their equivalents, the embodiments of the invention may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the invention may relate to individual features, systems, articles, materials, kits and/or methods described herein. Furthermore, if such features, systems, articles, materials, kits and/or methods are not mutually exclusive, any combination of two or more such features, systems, articles, materials, kits and/or methods comprises Within the scope of the invention of the present invention.

The above-described embodiments of the invention can be implemented in any of numerous ways. For example, some embodiments may be implemented using hardware, software, or a combination thereof. When any aspect of an embodiment is implemented at least in part in software, the software code can be executed on any suitable processor or collection of processors, whether provided on a single computer or distributed among multiple computers.

In this regard, various aspects of the present invention can be embodied at least in part as a computer-readable storage medium (or multiple computer-readable storage mediums) encoding one or more programs (e.g., a computer memory, one or more software disk, optical disk, optical disk, magnetic tape, flash memory, field programmable gate array or loop structure design in other semiconductor devices, or other tangible computer storage media or non-transitory media), the one or more programs Methods implementing various embodiments of the techniques discussed above are performed when executed on one or more computers or other processors. The computer-readable medium(s) may be portable so that the programs stored thereon may be loaded into one or Various aspects of the inventive techniques as discussed above may be implemented on a plurality of different computers or other processors.

In a general sense, the terms "program" or "software" are used herein to refer to any type of computer program that can be used to program a computer or other processor to implement aspects of the inventive technology as discussed above code or computer-executable instruction set. In addition, it should be understood that according to an aspect of this embodiment, one or more computer programs that perform the methods of the present technology need not reside on a single computer or processor when executed, but can be distributed in a modular manner Various aspects of the inventive technique are implemented in a number of different computers or processors.

Computer-executable instructions may take many forms, such as program modules, executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. In general, the functionality of the program modules may be combined or distributed as desired within various embodiments.

Furthermore, the techniques described herein may be embodied as a method for which at least one instance thereof is provided. The acts performed as part of the method may be ordered in any suitable manner. Accordingly, embodiments may be constructed in which acts are performed in an order different than that illustrated, which can include performing some acts simultaneously, even if shown as sequential acts in illustrative embodiments.

All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

The indefinite articles "a" and "an" as used herein in the specification and claims should be understood to mean "at least one" unless expressly indicated to the contrary.

As used herein in the specification and claims, the phrase "and/or" should be understood to mean "either or both" of the elements so conjoined, i.e., co-existing and in some cases Components that otherwise exist separately. Multiple elements listed using "and/or" should be construed in the same fashion, ie, "one or more" of the elements so conjoined. See Other elements may be present other than the elements specifically identified by the "and/or" clause, whether related or unrelated, to the elements specifically identified. Thus, as a non-limiting example, a reference to "A and/or B" when used in conjunction with open-ended language such as "comprises" may refer to only A in one embodiment (excluding B if desired). elements other than A); refer to only B in another embodiment (including elements other than A as required); refer to both A and B (including other elements as required) in yet another embodiment; and so on.

As used herein in the specification and claims, "or" should be understood as having the same meaning as "and/or" as defined above. For example, "or" or "and/or" when separating the items of a list should be construed as inclusive, that is, including several elements or at least one of the list of elements, but also including more than one, and Include additional items not listed as needed. Only terms expressly indicated to the contrary (such as "only one of") or "the only one of" or "consisting of" when used in claims shall refer to the inclusion The only one of several components or a list of components. In general, the term "or" as used herein should only be construed as indicating an exclusive term (such as "either", "one of", "only one of", " Exactly one of ...") (i.e., "either or the other but not both"). "Consisting essentially of" when used in the claims shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and claims, in reference to a list of one or more elements, the phrase "at least one" should be understood to mean any one of the elements selected from the list of elements or more of at least one element, but does not necessarily include at least one of the individual elements specifically listed in the element list and does not exclude any combination of elements in the element list. This definition also allows for the optional presence of elements other than those specifically identified in the list of elements to which the phrase "at least one" refers, whether related or unrelated to those specifically identified elements. Thus, as a non-limiting example, "at least one of A and B" (or equivalently "at least one of A or B", or equivalently "at least one of A and/or B") may In one embodiment, it refers to at least one One (and optionally includes elements other than B); in another embodiment refers to at least one that optionally includes more than one B and the absence of A (and optionally includes elements other than A); in yet another In the embodiments, it refers to at least one of at least one of A and at least one of B as needed (and other elements as needed) and the like.

In the claims as well as in the above specification, all transitional phrases (such as "includes", "comprises", "carries", "has", "contains", "relates to", "retains", "consists of" etc.) should be understood as open-ended, ie meant to include but not be limited to. Only the transitional phrases "consisting of" and "consisting essentially of" shall be closed or semi-closed transitional phrases, respectively, as stated in USPTO Handbook of Patent Examining Procedures Section 2111.03 .

200‧‧‧Extracorporeal loop

206‧‧‧Pump system

208‧‧‧Heat exchanger

210‧‧‧Injector components

212‧‧‧Vascular injection point

214‧‧‧blood

Claims (44)

A method for operating a flow congestion control system comprising: establishing flow through an extracorporeal circuit including a port for returning blood from the extracorporeal circuit to a region of the body A blood vessel; at least one injector member, which includes a lumen, the at least one injector member is structurally designed to cause blood to flow at a vessel injection point; an additional minimal conduction component, which is disposed on the at least one the proximal end of a distal tip of the injector member; and causing an injected flow from the at least one injector member to be at a flow rate such that a net or average countercurrent or forward flow is maintained at the at least one predetermined minimum flow rate. in the vessel external to the injector member; and setting a conduction by the additional minimum conduction element such that the flow rate within a blood pressure cycle of a heartbeat is higher than the minimum flow during at least a portion of a time of the heartbeat rate, and so that in each cycle of the heartbeat, the region of the blood vessel outside the at least one injector member is flushed with blood. The method of claim 1, wherein the additional minimum conductive element comprises an air bag. The method of claim 1, wherein the additional minimal conductive element comprises at least one of an atraumatic surface, a hydrophilic coating, or a drug coating. The method of claim 1, wherein the additional minimal conductive component comprises a bias valve, a discrete lumen, or a spring-actuated membrane having at least one opening formed therethrough. The method of claim 1, wherein the additional minimum conductive component comprises one or more bias valves coupled to a port of a lumen. The method of claim 1, further comprising: A first pressure sensor disposed at the distal end of the additional minimal conductive element; and a second pressure sensor disposed at the proximal end of the additional minimal conductive element. The method of claim 5, further comprising adding an amount of at least one of a drug or a medicament to the fluid injected through the at least one injector member. The method of claim 7, further comprising adjusting the concentration of the at least one of the drug or agent using pressure measurement and the addition of minimum conductance to produce the at least one of the drug or agent in a mixed distal flow For the desired concentration, the pressure measurements are made using the first pressure sensor and the second pressure sensor. A method for operating a flow congestion control system comprising: establishing flow through an extracorporeal circuit including a port for returning blood from the extracorporeal circuit to a region of the body a vessel at the location; an injector member coupled to the flow port, the injector member comprising a distal tip and a shaft having a lumen; a control shunt system comprising: at least one first pressure sensing device disposed on the proximal end of the distal tip; at least one second pressure sensor disposed on an outer surface of the shaft of the injector member; and an infusion rate source coupled to the Injector member to control a fluid flow from the distal tip of the injector member; within a time interval T , the fluid flow to be injected at the distal tip of the injector member using the injection flow rate source controlling to a predetermined flow rate mode; during the time interval T , recording pressure measurements using the first pressure sensor and the second pressure sensor; and indicating the pressure measurements and the predetermined flow rate mode using At least one of a proximal external conduction or a distal external conduction at the distal tip of the injector member is calculated. The method of claim 9, wherein the predetermined flow rate pattern includes a first constant flow rate within a first time interval t ₁ < T and a second time interval t ₂ < T is a second constant flow rate different from the first constant flow rate. The method of claim 10, wherein controlling the fluid flow comprises: controlling the fluid flow injected at the distal tip of the injector member using the injection flow rate source to within the _first time interval t1 the first constant flow rate; and controlling the flow of the fluid injected at the distal tip of the injector member using the injection flow rate source to the second constant flow rate during the _second time interval t2 . The method of claim 11, wherein recording the pressure measurements comprises: recording a first pressure measurement using the first pressure sensor and the second pressure sensor during the _first time interval t1 ; And during the _second time interval t2 , a second pressure measurement is recorded using the first pressure sensor and the second pressure sensor. The method of claim 12, wherein the distance of the injector member is calculated using data indicative of the first pressure measurements, the second pressure measurements, the first constant flow rate, and the second constant flow rate. The at least one of the proximal external conduction or the distal external conduction at the distal tip. The method of claim 9, wherein the second pressure sensor is disposed on the injector member at a distance from the proximal end of the distal tip that is greater than or approximately equal to about twice a diameter of the vessel the outer surface of the shaft. The method of claim 9, further comprising controlling the fluid flow injected at the distal tip of the injector member to maintain the flow rate at a value such that the proximal end of the additional minimum conduction element is flushed with blood flow A region of the vessel. The method of claim 9, further comprising controlling the flow so that at the distal tip The injected fluid flows according to a step function. The method of claim 9, wherein the second pressure sensor is positioned at a distance greater than about 1.0 cm from the proximal end of the distal tip. The method of claim 9, further comprising adding an amount of at least one of a drug or a medicament to the fluid injected through the at least one injector member. The method of claim 18, further comprising adjusting a concentration of the at least one of drug or agent using the pressure measurements and the measured proximal external conduction to produce drug or drug in a mixed distal flow. A desired concentration of the at least one of the medicaments, the pressure measurements are made using the first pressure sensor and the second pressure sensor. A system for flow congestion control comprising: an extracorporeal circuit including a port for returning blood from the extracorporeal circuit to a vessel in a region of the body; and an injector member , which includes a lumen, the at least one injector member is structured to cause blood to flow at a vascular injection point; a control shunt system, which includes: a first pressure sensor, which is used to measure the indication a first parameter of flow proximal to a distal tip of the injector member; a second pressure sensor for measuring a second parameter indicative of flow, the second sensor being in accordance with The proximal end of the distal tip is disposed at the proximal end of the injector member at a predetermined distance; and an infusion flow rate source coupled to the extracorporeal circuit to induce a predetermined flow rate at the vascular infusion point Injection flow in rate mode. The system of claim 20, wherein the injection rate source is a syringe pump or a rotary pump. The system of claim 20, further comprising a flow control module programmed to respond to infusion flow at the vascular injection point according to the predetermined flow rate pattern based on indicating the first Data from the measurements of the pressure sensor and the second pressure sensor calculate an indication of a proximal external conduction. The system of claim 20, wherein the flow control module is further programmed to: generate a signal indicative of a flow parameter to adjust blood flow or maintain blood flow in the vessel at a predetermined flow rate value. The system of claim 20, wherein the predetermined distance is a distance from the proximal end of the distal tip that is greater than or approximately equal to about twice a diameter of the vessel. The system of claim 20, wherein the control shunt system is structured to add an amount of at least one of a drug or medicament to the fluid injected through the injector member. A system for flow congestion control comprising: an extracorporeal circuit including a port for returning blood from the extracorporeal circuit to a vessel at a region of the body; and an injector member, it includes a distal tip; a control shunt system, it includes: a first pressure sensor, it is arranged on the proximal end of this distal tip of this at least one injector member; a second pressure sensor disposed at an outer surface of the at least one injector member at a predetermined distance from the proximal end of the distal tip; an injection flow rate source coupled to the injector member to inject flow from the distal tip the flow rate of the fluid is controlled to a predetermined flow rate pattern; and a console comprising at least one processing unit programmed to: receive an indication during a time interval T of the blood flow according to the using data from pressure measurements made by the first pressure sensor and the second pressure sensor with a predetermined flow rate pattern injected at the distal tip; and using data indicative of the pressure measurements and the predetermined flow rate pattern Flow pattern data for calculating at least one of a proximal external conduction or a distal external conduction at the distal tip of the at least one injector member. The system of claim 26, wherein the predetermined flow rate pattern includes a first constant flow rate during a first time interval t ₁ < T and a second time interval t ₂ < T is a second constant flow rate different from the first constant flow rate. The system of claim 27, wherein the at least one processing unit is further programmed to cause the injection flow rate source: the injection to be injected at the distal tip of the injector member during the _first time interval t1 fluid flow is controlled to the first constant flow rate; and during the _second time interval t2 , the fluid flow to be injected at the distal tip of the injector member is controlled to the second constant flow rate. The system of claim 28, wherein the at least one processing unit is further programmed to record a first amount of pressure using the first pressure sensor and the second pressure sensor during the _first time interval t1 and within the _second time interval t2 , recording a second pressure measurement using the first pressure sensor and the second pressure sensor. The system of claim 29, wherein the distance of the injector member is calculated using data indicative of the first pressure measurements, the second pressure measurements, the first constant flow rate, and the second constant flow rate. The at least one of the proximal external conduction or the distal external conduction at the distal tip. The system of claim 26, wherein the console further comprises a display unit for displaying an indication of at least one of the proximal external conduction or the distal external conduction. The system of claim 26, wherein the at least one processing unit is further programmed to calculate the proximal external conduction or the distal A projection of at least one of the external conductions. The system of claim 26, wherein the injection flow rate source is a volumetric flow controller configured to control the flow such that fluid injected at the distal tip flows according to a step function. The system of claim 26, wherein the second pressure sensor is disposed at a distance greater than about 1.0 cm from the proximal end of the distal tip. The system of claim 26, wherein the at least one processing unit is further programmed to be based on an amount of at least one of a drug or agent added to a fluid injected through the injector member and the proximal external conduction or the A value of at least one of the distal external conductance, a concentration of the at least one of a drug or agent in a mixed distal stream is calculated. A method for operating a flow congestion control system comprising: coupling an extracorporeal circuit to a portion of a body, the extracorporeal circuit including a port for returning blood from the extracorporeal circuit to a body A vessel at one region; an injector member coupled to the flow port, the injector member comprising a distal tip and a shaft with a lumen; at least one first pressure sensor disposed at the proximal end of the distal tip; at least one second pressure sensor disposed on an outer surface of the shaft of the injector member; and an injection flow rate source coupled to the injection member to control a fluid flow from the distal tip of the injector member; controlling the flow of fluid injected at the distal tip of the injector member using the injection flow rate source during a _first time interval T to a predetermined flow rate pattern; during the first time interval T ₁ , recording pressure measurements using the first pressure sensor and the second pressure sensor; indicating the pressure measurements and the predetermined flow rate pattern using calculating a value of a proximal external conductance at the distal tip of the injector member; calculating an external flow rate using the first and second pressure measurements and the calculated proximal external conduction, and use the external flow rate to calculate the ratio of infused flow rate to external flow rate in the distal mixing fluid; and control the amount of drug or agent added to the infused fluid, and use the infused flow rate to external flow rate The calculated ratio of ratios adjusts the amount to achieve a specified concentration of drug or agent in the mixed distal fluid. The method of claim 36, wherein the predetermined flow rate pattern includes a first constant flow rate during a first time interval t ₁ < T and a second time interval t ₂ < T is a second constant flow rate different from the first constant flow rate. The method of claim 37, wherein controlling the fluid flow comprises: controlling the fluid flow injected at the distal tip of the injector member using the injection flow rate source to within the _first time interval t1 the first constant flow rate; and controlling the flow of the fluid injected at the distal tip of the injector member using the injection flow rate source to the second constant flow rate during the _second time interval t2 . The method of claim 36, wherein the recording the pressure measurements comprises: recording a first pressure measurement using the first pressure sensor and the second pressure sensor during the _first time interval t1 ; And during the _second time interval t2 , a second pressure measurement is recorded using the first pressure sensor and the second pressure sensor. The method of claim 39, wherein the distance of the injector member is calculated using data indicative of the first pressure measurements, the second pressure measurements, the first constant flow rate, and the second constant flow rate. The at least one of the proximal external conduction or the distal external conduction at the distal tip. The method of claim 36, wherein the second pressure sensor is disposed on the injector member at a distance from the proximal end of the distal tip that is greater than or approximately equal to about twice a diameter of the vessel the outer surface of the shaft. The method of claim 36, further comprising controlling the fluid flow injected at the distal tip of the injector member to maintain the flow rate at a value such that the proximal end of the externally applied minimum conduction element is flushed with blood flow A region of the vessel. The method of claim 36, further comprising controlling the flow such that fluid injected at the distal tip flows according to a step function. The method of claim 36, wherein the second pressure sensor is positioned at a distance greater than about 1.0 cm from the proximal end of the distal tip.

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