System and method having transition phase in multi-phase infusion protocol - Patents.com

Abstract

To solve the problem of causing less than optimal injection boluses or optimal injection volumes and / or the problem of operation of a fluid delivery system resulting in relatively large amounts of wasted fluid.SOLUTION: A method of realizing a multi-phase fluid injection to a patient via a fluid injector comprising two or more syringes includes: injecting a first fluid of the fluid injection from at least a first syringe at a first predetermined flow rate, where the first fluid has a first viscosity; injecting an initial portion of a second fluid from at least a second syringe at an intermediate flow rate different than a second predetermined flow rate for a specified time, the second fluid having a second viscosity different from the first viscosity; and injecting a remaining portion of the second fluid of the fluid injection at a flow rate at the second predetermined flow rate. A fluid injector system configured for realizing a multi-phase fluid injection is disclosed.SELECTED DRAWING: Figure 7A

Description

[Technical field]

[0001] REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 552,494, entitled "SYSTEM AND METHOD HAVING TRANSITION STAGES IN MULTI-PHASE INFUSION PROTOCOLS," filed August 31, 2017.

[0002] Background of the disclosure FIELD OF THE DISCLOSURE The present disclosure relates generally to systems and methods for controlling a liquid injector, and more particularly to systems and methods for controlling a liquid injector utilizing a multi-phase injection protocol having transition phases. [Background technology]

[0003] In many medical diagnostic and therapeutic procedures, a practitioner, such as a physician, injects one or more medical fluids into a patient. In recent years, many infusion systems having injector-actuated syringes and fluid injectors for pressurized injection of fluids such as contrast solutions (often simply referred to as "contrast"), flushing agents such as saline or lactated Ringer's solution, and other medical fluids have been developed for use in procedures such as angiography (CV), computed tomography (CT), ultrasound, magnetic resonance imaging (MRI), positron emission tomography (PET), and other imaging studies. Broadly speaking, these infusion systems are designed to infuse a preset volume of fluid at a desired flow rate. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2016 / 172467 Brochure [Patent Document 2] International Publication No. 2015 / 164783 Brochure [Patent Document 3] U.S. Pat. No. 5,383,858 [Patent Document 4] U.S. Patent No. 7,553,294 [Patent Document 5] U.S. Pat. No. 7,666,169 [Patent Document 6] U.S. Patent No. 9,173,995 [Patent Document 7] U.S. Pat. No. 9,199,033 [Patent Document 8] U.S. Pat. No. 9,474,857 [Patent Document 9] International Publication No. 2016 / 191485 Brochure [Patent Document 10] International Publication No. 2016 / 112163 Brochure [Patent Document 11] U.S. Patent No. 6,322,535 [Patent Document 12] U.S. Patent No. 6,652,489 [Patent Document 13] U.S. Patent No. 9,173,995 [Patent Document 14] U.S. Pat. No. 9,199,033 Summary of the Invention [Problem to be solved by the invention]

[0005] The actual flow rate (i.e., volume of infusion) of fluid delivered to a patient is targeted to be as close as possible to the desired flow rate (i.e., volume of infusion). However, the actual volume delivered by the infusion system is a function of many factors due to the overall impedance and capacitance of the infusion system. In a particular infusion procedure, the impedance and capacitance of the infusion system may cause variations in fluid flow, such as excess or insufficient fluid flow (i.e., over or under volume infusion) from the desired flow rate (i.e., volume of infusion), especially when switching from one fluid type to another.

[0006] Although there are various techniques for characterizing the performance of an infusion system and correlating the desired performance with the actual performance in terms of fluid flow rate and volume infused, these techniques do not address the difference between the desired performance and the actual performance due to the impedance and / or capacitance of the infusion system in a readily conceivable way. The conclusion is that existing techniques are unable to address the under- or over-infusion of fluid due to the impedance and / or capacitance of the system. This can result in less than optimal bolus or injection volumes and / or a relatively large amount of fluid being wasted after operation of the infusion system. [Means for solving the problem]

[0007] In one example of the disclosure, a method for providing a multi-stage fluid infusion to a patient via a fluid injector having two or more fluid reservoirs is described, which may include injecting a first fluid of the fluid infusion from at least a first fluid reservoir, the first fluid having a first viscosity, the first fluid being infused to the patient at a first predetermined flow rate, injecting an initial portion of at least a second fluid of the fluid infusion from at least a second fluid reservoir, the second fluid having a second viscosity different from the first viscosity, the initial portion of the second fluid being infused to the patient using a flow rate profile for a specified intermediate time interval different from the second predetermined flow rate, and injecting a remaining portion of the second fluid of the fluid infusion at a flow rate at least corresponding to the second predetermined flow rate.

[0008] In certain embodiments, the first viscosity is greater than the second viscosity. The first and second fluids may be contrast media, saline, lactated Ringer's solution, or other medical fluids. In certain embodiments, the first fluid may be selected from the group consisting of contrast media, a mixture of contrast media in a specific ratio and saline or other flushing fluid such as water or lactated Ringer's solution, and the second fluid may be selected from the group consisting of saline or other flushing fluid such as water or lactated Ringer's solution, and a mixture of contrast media in a second specific ratio and saline or other flushing fluid such as water or lactated Ringer's solution. According to some aspects, the second predetermined flow rate may be substantially the same as the first predetermined flow rate.

[0009] According to various embodiments, the flow rate profile of at least the first portion of the second fluid may be different from the first predetermined flow rate and / or the second predetermined flow rate. In some embodiments, the flow rate profile of at least the first portion of the at least second fluid is infused at a flow rate less than the first predetermined flow rate. In other embodiments, the flow rate profile of at least the first portion of the at least second fluid is infused at a flow rate that varies between zero and the first or second predetermined flow rate over a specified intermediate time interval. For example, the flow rate profile of at least the first portion may start at a low flow rate and increase over a specified intermediate time interval, such increase leading to the second predetermined flow rate by the end of the at least the first portion of the second fluid.

[0010] According to various embodiments of the methods described herein, infusing at least an initial portion of the second fluid may comprise infusing at least an initial portion of the second fluid at an intermediate flow rate less than a second predetermined flow rate for a designated intermediate time interval selected to allow a remaining portion of the first fluid to pass through the fluid line to the patient before initiating the step of infusing the remaining portion of the second fluid, the designated intermediate time interval being based on the system configuration, i.e., capacitance of at least one of the first and second fluid reservoirs, length of the fluid line, diameter of the fluid line, volume of the fluid line, length of the catheter, diameter of the catheter, volume of the catheter, and any combination thereof. In various embodiments of the methods, the volume of the initial portion of the second fluid of the fluid infusion may be determined by one or more of the volume capacity of the fluid line between the second fluid reservoir and the patient (including, where appropriate, catheter volume capacity), capacitance of at least one of the first and second fluid reservoirs, and infusion system compliance.

[0011] In certain embodiments, the method may further comprise a system user inputting a flow rate profile for the second fluid including the transition phase based at least in part on one or more parameters selected from the group consisting of a table of injection protocols, a first phase flow rate, a second phase flow rate, a transition flow rate, a catheter volume, a catheter diameter, a catheter length, a volume of a fluid line between the fluid reservoir and the patient, a fluid line diameter, a fluid line length, a viscosity of the first fluid, a viscosity of the second fluid, a temperature of the first fluid, a temperature of the second fluid, a programmed volume of the first fluid to be infused, and a programmed volume of the second fluid to be infused. The tables may be provided by a system manufacturer and programmed into a processor associated with the fluid injector system, or may be independently developed by a system user or other third party for use with various injection protocols of the fluid injection system.

[0012] According to certain embodiments, the flow profile of the initial portion is selected to minimize flow deviation over a specified intermediate time interval. In certain embodiments, the flow profile of the initial portion is selected according to the formula: Q(Transition) = Q(Program Setting) - Q(Adjusted) where Q(Transition) is the desired flow profile across the transition from the first fluid to the at least second fluid by adjusting the movement (adjusting speed over distance) of the drive member to control the flow of fluid out of the catheter tip, Q(Programmed) is the desired flow profile of the at least second fluid, and Q(Adjusted) is the adjustment in the flow rate of the second fluid required to result in a fluid flow rate from the catheter that is substantially similar to Q(Programmed) as a result of Q(Transition) at the transition between the first fluid and the at least second fluid. In other embodiments, the flow profile of the first portion is calculated based on the formula Q(t) = Q(p) - (C(1) - C(2)) / t(t) where Q(t) is the intermediate flow rate, Q(p) is the second predefined flow rate, C(1) is the steady state system compliance at the first fluid stage, C(2) is the system compliance during the second fluid infusion, and t(t) is the derived time to infuse a volume associated with the system compliance (C(2)). According to various embodiments, the system compliance during the first fluid infusion comprises a first compliance coefficient associated with one or more of the first fluid reservoir, the first infusion mechanism, and a set of tubing in operative fluid communication with the first fluid reservoir, and the system compliance during the second fluid infusion comprises a second compliance coefficient associated with one or more of the second fluid reservoir, the second infusion mechanism, and a set of tubing in operative fluid communication with the second fluid reservoir. The system compliance of the first reservoir and / or at least the second reservoir may be measured, for example, using a flow sensor in the fluid pathway between the one or more reservoirs and the catheter. Alternatively, one or both of the system compliances of the first reservoir and / or at least the second reservoir may be predicted based on coefficients of the fluid infuser, the first or second fluid reservoir, and the first or second fluid, respectively.

[0013] According to various embodiments of the present disclosure, the first and second fluid reservoirs may be independently selected from the group consisting of a syringe, a peristaltic pump, and a compressible bag. In certain embodiments, the first fluid reservoir is a first syringe operably connected to a first drive member of the fluid injector, and the at least second fluid reservoir is at least a second syringe operably connected to at least a second drive member of the fluid injector.

[0014] According to another embodiment, the present disclosure describes a fluid injector system for providing a multi-stage fluid injection to a patient, the fluid injector system including at least one first syringe configured to receive a first fluid of the multi-stage fluid injection, the first fluid having a first viscosity, at least one first drive member operatively connected to the at least one first syringe, the at least one first drive member operable to dispense the first fluid of the multi-stage fluid injection, at least one second syringe configured to receive a second fluid of the multi-stage fluid injection, the second fluid having a second viscosity different from the first viscosity, and at least one second drive member operatively connected to the at least one second syringe, the at least one second drive member operable to dispense the first fluid of the multi-stage fluid injection. The one second piston may comprise at least one second drive member operable to dispense a second fluid of the multi-stage fluid injection; fluid lines connected to the at least one first syringe and the at least one second syringe and configured to infuse at least one of a first fluid of the multi-stage fluid injection from the at least one first syringe to the patient and a second fluid of the multi-stage fluid injection from the at least one second syringe to the patient; and a control device configured to control movement of the first drive member associated with the at least one first syringe and movement of the at least one second drive member associated with the at least one second syringe to control the infusion of the first and second fluids of the multi-stage fluid injection to the patient. The control device may be configured to control the first drive member to inject the first fluid at a first predetermined flow rate, control the at least one second drive member to inject at least a first portion of the fluid injection from the at least one second syringe at an intermediate flow rate profile for a specified intermediate time that is different from the second predetermined flow rate, and inject a remaining portion of the second fluid corresponding to at least the second predetermined flow rate, the second fluid having a second viscosity different from the first viscosity.

[0015] According to various embodiments, the first viscosity is greater than the second viscosity. The first and second fluids may be contrast media, saline, lactated Ringer's solution, other flushing fluids, or other medical fluids. In certain embodiments, the first fluid may be selected from the group consisting of contrast media and a mixture of contrast media and saline in a specific ratio, and the second fluid may be selected from the group consisting of saline, lactated Ringer's solution, and a mixture of contrast media and saline in a second specific ratio. According to some aspects, the second predetermined flow rate may be substantially the same as the first predetermined flow rate.

[0016] In various embodiments of the fluid infuser system, the first preset flow rate may be substantially the same as the second preset flow rate. In other embodiments, the flow rate profile of at least an initial portion of at least the second fluid may be infused at a rate less than the first preset flow rate, or the flow rate profile of at least an initial portion of at least the second fluid may be infused at a rate that varies between zero and the first preset flow rate or between zero and the second preset flow rate over a specified intermediate time interval. According to some embodiments, the first preset flow rate may be greater than the second preset flow rate.

[0017] According to various embodiments of the fluid injector system, the control device may be configured to set the timing of injection of at least a first portion of the second fluid, comprising injecting at least a first portion of the second fluid at an intermediate flow rate less than a second predetermined flow rate for a specified intermediate time interval, the specified intermediate time interval being selected to allow a remaining portion of the first fluid to pass through the fluid line to the patient before commencing the step of injecting the remaining portion of the second fluid, the specified intermediate time interval being based on one or more of the system configuration, i.e., the capacitance of at least one of the first and second fluid reservoirs, the length of the fluid line, the diameter of the fluid line, the volume of the fluid line, the capacitance of the fluid line and associated catheter, and any combination thereof.

[0018] According to some embodiments of the liquid injection system, the flow profile of the initial portion can be expressed as follows: Q(Transition) = Q(Program Setting) - Q(Adjusted) where Q(Transition) is the desired flow rate profile across the transition between the first and at least the second fluid by adjusting the movement of the drive member (adjusting the speed over the distance) to control the flow of fluid out of the catheter tip, Q(Programmed) is the desired flow rate profile of the at least the second fluid, and Q(Adjusted) is the adjustment in the flow rate of the second fluid required to result in a fluid flow rate from the catheter that is substantially similar to Q(Programmed) as a result of Q(Transition) at the transition between the first and at least the second fluid. According to certain embodiments, the intermediate time can be a consideration of the time it takes for the remaining volume of the first fluid to be infused from the fluid line, e.g., the time obtained by dividing the volume of the fluid line and catheter by the programmed flow rate.

[0019] According to another embodiment of the injector system, the flow profile of the initial portion is expressed by the formula: Q(t) = Q(p) - (C(1) - C(2)) / t(t) where Q(t) is the intermediate flow rate, Q(p) is the second predefined flow rate, C(1) is the steady-state system compliance at the first fluid stage, C(2) is the system compliance during the second fluid infusion, and t(t) is the derived time to infuse the volume associated with the system compliance (C(2)).

[0020] Various aspects of systems and methods for controlling a liquid injector utilizing a multi-stage injection protocol having transition stages are disclosed in one or more of the following numbered paragraphs.

[0021] Item 1. A method for providing a multi-stage fluid infusion to a patient via a fluid injector having two or more fluid reservoirs, comprising the steps of injecting a first fluid of the fluid infusion from at least a first fluid reservoir, the first fluid having a first viscosity, the first fluid being infused to the patient at a first predetermined flow rate; injecting an initial portion of at least a second fluid of the fluid infusion from at least a second fluid reservoir, the second fluid having a second viscosity different from the first viscosity, the initial portion of the second fluid being infused to the patient using a flow rate profile different from the second predetermined flow rate for a specified intermediate time interval or intermediate fluid volume; and injecting a remaining portion of the second fluid of the fluid infusion at a flow rate at least corresponding to the second predetermined flow rate.

[0022] Item 2. The method of item 1, wherein the first viscosity is greater than the second viscosity.

[0023] Item 3. The method of item 1 or 2, wherein the first liquid is selected from the group consisting of a contrast agent and a mixture of a contrast agent and saline in a specific ratio, and the second liquid is selected from the group consisting of saline and a mixture of a second specific ratio of a contrast agent and saline.

[0024] Clause 4. The method of any one of clauses 1 to 3, wherein the second predetermined flow rate is approximately the same as the first predetermined flow rate.

[0025] Clause 5. The method of any one of clauses 1 to 4, wherein the flow rate profile of at least a first portion of at least the second liquid is infused at a flow rate that is less than the first predetermined flow rate.

[0026] Clause 6. The method of any one of clauses 1 to 5, wherein the flow rate profile of at least an initial portion of at least the second liquid is infused at a flow rate that varies between zero and a second predefined flow rate over a specified intermediate time interval.

[0027] Clause 7. The method of any one of clauses 1 to 6, wherein the step of injecting at least a first portion of the second fluid comprises injecting at least a first portion of the second fluid at an intermediate flow rate less than a second predetermined flow rate for a specified intermediate time interval, the specified intermediate time interval being selected to allow a remaining portion of the first fluid to pass through the fluid line to the patient before commencing the step of injecting the remaining portion of the second fluid, the specified intermediate time interval being based on one or more of the system configuration, i.e., capacitance of at least one of the first and second fluid reservoirs, length of the fluid line, diameter of the fluid line, volume of the fluid line, length of the catheter, diameter of the catheter, volume of the catheter, and any combination thereof.

[0028] Clause 8. The method of any one of clauses 1 to 6, wherein the volume of the initial portion of the second fluid infusion is determined by one or more of the volume capacity of a fluid line between the second fluid reservoir and the patient, the capacitance of at least one of the first and second fluid reservoirs, and the infusion system compliance.

[0029] Clause 9. The method of any one of clauses 1 to 8, further comprising a step of a system user inputting a flow rate profile for the second fluid based at least in part on one or more parameters selected from the group consisting of a table of infusion protocols, a first phase flow rate, a second phase flow rate, a transition flow rate, a catheter volume, a catheter diameter, a catheter length, a volume of a fluid line between the fluid reservoir and the patient, a fluid line diameter, a fluid line length, a temperature of the first fluid, a temperature of the second fluid, a viscosity of the first fluid, a viscosity of the second fluid, a programmed volume of the first fluid to be infused, and a programmed volume of the second fluid to be infused.

[0030] Clause 10. The method of any one of clauses 1 to 9, wherein the flow profile of the initial portion is selected to minimize deviations in flow rate over a specified intermediate time interval.

[0031] 11. The flow rate profile of the first part is given by Eq. Q(Transition) = Q(Program Setting) - Q(Adjusted) where Q(Transition) is a desired flow profile at the transition between the first fluid and at least the second fluid, Q(Programmed) is a desired flow profile of the first fluid and at least the second fluid, and Q(Adjusted) is an adjustment to the flow rate of the second fluid required for the transition between the first fluid and at least the second fluid to be approximately similar to Q(Transition) at the transition between the first fluid and at least the second fluid, i.e., the flow rate at the catheter tip,

[0032] 12. The flow rate profile of the first part is given by Eq. Q(t) = Q(p) - (C(1) - C(2)) / t(t) where Q(t) is the intermediate flow rate, Q(p) is the second predetermined flow rate, C(1) is the steady state system compliance at the first fluid stage, C(2) is the system compliance during the second fluid infusion, and t(t) is the derived intermediate time to infuse a volume related to the system compliance (C(2)).

[0033] Clause 13. The method of clause 12, wherein the system compliance during the first fluid injection comprises a first compliance coefficient associated with one or more of the first fluid reservoir, the first infusion mechanism, and a set of tubing in operative fluid communication with the first fluid reservoir, and the system compliance during the second fluid injection comprises a second compliance coefficient associated with one or more of the second fluid reservoir, the second infusion mechanism, and a set of tubing in operative fluid communication with the second fluid reservoir.

[0034] Clause 14. The method of any one of clauses 1 to 13, wherein the first fluid reservoir is a first syringe operably connected to a first drive member of the fluid injector, and the at least second fluid reservoir is at least a second syringe operably connected to at least a second drive member of the fluid injector.

[0035] Clause 15. A fluid injector system for providing a multi-stage fluid injection to a patient, comprising at least one first syringe configured to receive a first fluid of the multi-stage fluid injection, the first fluid having a first viscosity, at least one first drive member operatively connected to the at least one first syringe, the at least one first drive member operable to dispense the first fluid of the multi-stage fluid injection, and at least one first drive member operable to dispense the second fluid of the multi-stage fluid injection. at least one second syringe configured to receive a fluid, the second fluid having a second viscosity different from the first viscosity; at least one second drive member operably connected to the at least one second syringe, the at least one second piston operable to dispense the second fluid of the multi-stage fluid injection; and at least one second drive member connected to the at least one first syringe and the at least one second syringe and operable to dispense the second fluid of the multi-stage fluid injection. a fluid line configured to infuse at least one of a first fluid of a multi-stage fluid injection from a first syringe to a patient and a second fluid of the multi-stage fluid injection from at least one second syringe to the patient; and a control device configured to control movement of a first drive member associated with the at least one first syringe and movement of at least one second drive member associated with the at least one second syringe to control the infusion of the first and second fluids of the multi-stage fluid injection to the patient, wherein the control device is configured to control the first drive member to infuse the first fluid at a first predetermined flow rate, control the at least one second drive member to infuse a first portion of at least a second fluid of the fluid injection from the at least one second syringe at an intermediate flow rate profile different from the second predetermined flow rate for a specified intermediate time or intermediate fluid volume, and infuse a remaining portion of the second fluid at least corresponding to the second predetermined flow rate, wherein the second fluid has a second viscosity different from the first viscosity.

[0036] Clause 16. The fluid injector system of clause 15, wherein the first viscosity exceeds the second viscosity.

[0037] Clause 17. The liquid injector system of clause 15 or clause 16, wherein the first predetermined flow rate is substantially the same as the second predetermined flow rate.

[0038] Clause 18. A liquid infuser system as described in any one of clauses 15 to 17, wherein the flow rate profile of at least an initial portion of at least the second liquid is infused at a flow rate less than the first predetermined flow rate, or the flow rate profile of at least an initial portion of the at least second liquid is infused at a flow rate that varies between zero and the first predetermined flow rate or the second predetermined flow rate over a specified intermediate time interval.

[0039] Clause 19. The liquid injector system of any one of clauses 15 to 18, wherein the control device is configured to set timing of injection of at least a first portion of the second liquid, comprising injecting at least a first portion of the second liquid at an intermediate flow rate less than a second predetermined flow rate for a specified intermediate time interval, the specified intermediate time interval being selected to allow a remaining portion of the first liquid to pass through the liquid line to the patient before commencing the step of injecting the remaining portion of the second liquid, the specified intermediate time interval being based on system configuration, i.e., capacitance of at least one of the first and second liquid reservoirs, length of the liquid line, diameter of the liquid line, volume of the liquid line, length of the catheter, diameter of the catheter, volume of the catheter, and any combination thereof.

[0040] Item 20. A liquid injection system as described in any one of items 15 to 19, wherein the first liquid is selected from the group consisting of a contrast agent and a mixture of a contrast agent and saline in a specific ratio, and the second liquid is selected from the group consisting of saline and a mixture of a contrast agent and saline in a second specific ratio.

[0041] 21. The flow profile of the first part is given by Eq. Q(Transition) = Q(Program Setting) - Q(Adjusted) where Q(Transition) is a desired flow rate profile at the transition between the first fluid and at least the second fluid, Q(Programmed) is a desired flow rate profile of the first fluid and at least the second fluid, and Q(Adjusted) is an adjustment to the flow rate of the second fluid required for the Q(Transition) at the transition between the first fluid and at least the second fluid, i.e., the flow rate at the catheter tip to be approximately equal to Q(Programmed).

[0042] 22. The flow rate profile of the first part is given by Eq. Q(t) = Q(p) - (C(1) - C(2)) / t(t) 21. The fluid infusion system of any one of claims 15 to 20, wherein Q(t) is an intermediate flow rate, Q(p) is a second predetermined flow rate, C(1) is the system compliance during the first fluid infusion, C(2) is the system compliance during the second fluid infusion, and t(t) is a derived intermediate time to infuse a volume of a first portion of the second fluid infusion.

[0043] These and other features and characteristics of the present disclosure, as well as the method of operation and function of the associated elements and combinations of parts of construction and economy of manufacture will become apparent from a consideration of the following description and the appended claims, taken in conjunction with the accompanying drawings, all of which form a part of this specification, in which like reference numerals indicate corresponding parts of the various views, it being of course expressly understood that the drawings are for the purpose of illustration and description only. [Brief description of the drawings]

[0044] [Figure 1] FIG. 1 is a perspective view of an infusion system according to an example of the present disclosure. [Diagram 2] 2 is a cross-sectional view of a syringe configured for use with the infusion system of FIG. 1. [Diagram 3] FIG. 1 is a perspective view of an infusion system according to another example of the present disclosure. [Figure 4]4 is a cross-sectional view of a syringe configured for use with the infusion system of FIG. 3. [Diagram 5] FIG. 1 is a perspective view of an infusion system according to another example of the present disclosure. [Figure 6] FIG. 6 is a front perspective view of a multi-use disposable system configured for use with the infusion system of FIG. [Figure 7A] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7B] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7C] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7D] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7E] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7F] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7G] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7H] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 7I] 1 illustrates one embodiment of a flow profile including transition stages by controlling the motor speed of an infusion system during a multi-stage injection. [Figure 8] 13 is a graph comparing measured flow rates for a multi-stage fluid injection during a stage transition with measured flow rates for a multi-stage injection during a transition stage. [Figure 9] FIG. 13 is a step diagram for determining the derivation of the steady state pressure for the second stage of a multi-stage fluid injection. [Figure 10] 1 is an exemplary look-up table for deriving limit and steady state pressures for multi-stage fluid injection. [Figure 11] 1 is a graph of an exemplary formula for deriving steady-state pressure for multi-stage fluid injection. [Figure 12] 1 is a graphical representation of a surface corresponding to a compliance equation for calculating capacitance. [Figure 13] FIG. 1 illustrates an overall workflow for determining an injection protocol including transition steps according to one embodiment. [Figure 14] 6 illustrates a specific implementation of an injection protocol including the transition phase of the injector shown in FIG. 5. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] As used in the specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0046] For purposes of the following description, the terms "top," "bottom," "right," "left," "vertical," "horizontal," "upper," "lower," "transverse," "longitudinal," and derivatives thereof shall refer to the disclosure as oriented in the drawings.

[0047] Various other orientations are contemplated by the present invention, and spatial and directional terms such as "left," "right," "inside," "outside," "up," and "down" are not to be considered limiting.

[0048] All numbers used in the specification and claims are to be understood as being modified in all instances by the term "about," which means a range of plus or minus ten percent of the stated value.

[0049] Unless otherwise indicated, all ranges or ratios disclosed in this application are to be understood to include all subranges or subratios subsumed therein. For example, a range of "1 to 10" or ratio of "1 / 10" is to be considered to include all subranges between the minimum value of 1 and the maximum value of 10 (inclusive). That is, all subranges or subratios begin with a minimum value of 1 or greater and end with a maximum value of 10 or less. Examples include, but are not limited to, 1 to 6.1 (1 / 6.1), 3.5 to 7.8 (3.5 / 7.8), and 5.5 to 10 (5.5 / 10).

[0050] The term "at least" means "more than or equal to."

[0051] The term "comprise" is synonymous with "comprise." "Comprise" includes "consisting of" and "consisting essentially of."

[0052] The term "proximal" when used in reference to a syringe and / or plunger refers to the portion of the syringe and / or plunger closest to the injector when the syringe and / or plunger is oriented to be connected to the injector. The term "distal" refers to the portion of the syringe and / or plunger furthest from the injector when the syringe and / or plunger is oriented to be connected to the injector. The term "radial" refers to a direction in a cross-sectional plane perpendicular to a longitudinal axis of the syringe, plunger and / or piston extending between the proximal and distal ends. The term "circumferential" refers to a direction about the inner or outer surface of a sidewall of the syringe, plunger and / or piston. The term "axial" refers to a direction along a longitudinal axis of the syringe, plunger and / or piston extending between the proximal and distal ends. The term "open" as applied to an infusion component means that the system is in fluid communication with an outlet, for example, through a nozzle or through an open end of a tubing component or catheter. In an open system, fluid flow may be restricted by forcing the fluid through a small diameter fluid path where the flow is determined by physical parameters of the system and the fluid, such as, for example, the diameter of the tubing, the constriction of the fluid path, the applied pressure, and the viscosity. The term "closed" as applied to an infusion element means that the system is not in fluid communication with an outlet where the fluid flow is stopped, for example, by a valve, such as a stopcock, high cracking pressure valve, pinch valve, etc. The term "slack" as used in this application means mechanical slack, including gaps between parts, mechanical component compression under load (e.g., due to applied pressure), and clearance and lost motion of mechanisms caused by deflection of mechanical components under load (e.g., due to applied pressure), resulting in a delay in pressurized infusion of fluid from the time of fluid injection after application of a force.

[0053] It is to be understood that the present disclosure contemplates alternative examples and sequences of steps, except where expressly stated to the contrary. It is also to be understood that the specific devices and processes illustrated in the accompanying drawings and described in the following specification are merely exemplary embodiments of the present disclosure. Hence, specific dimensions and other physical characteristics relating to the examples disclosed herein are not to be considered as limiting.

[0054] Characterizing the impedance of an infusion system to minimize the difference between desired and actual infusion system performance requires consideration of how energy from the energy source is used in the system and how it moves through the system. Energy output or loss from an infusion system may take the form of heat loss due to frictional forces and work done in the infusion system. For example, some of the energy carried by the pressurized fluid while being infused through a catheter under pressure is lost through resistive, frictional, or dissipative heating of the fluid. In addition, infusing fluid under pressure may also increase the potential energy of the system in terms of an overall increase in the volume of the system components or an increase in compressive forces on the system components, as described herein. Furthermore, the kinetic energy of the pressurized fluid moving through the infusion system may affect the overall performance of the infusion system. For example, inertial forces moving the contrast agent and expansion of the containers and / or tubing associated with the system may cause a phase misalignment between the movement of the syringe plunger in the injector syringe and the movement of the contrast agent from the catheter to the patient.

[0055] High injection pressures, which can be as high as 1,200 psi in some angiography procedures, can cause expansion, deflection, and compression of various components of the infusion system, such as the syringe, tubing connected to the patient, and components of the fluid injector. These can occur to such an extent that the volume of fluid in the syringe and tubing may exceed the desired volume selected to be infused in the injection procedure. This increase in volume of fluid occurs due to the capacitance of the system. The total system capacitance (also referred to as compliance or elasticity) represents the amount of fluid trapped during expansion of the components of the infusion system (i.e., the change in volume, such as volume overage). In general, capacitance is directly correlated to the injection pressure and directly correlated to the pressurized fluid volume of the contrast and saline in the syringe. For example, the larger the volume, the larger the internal surface area of ​​the syringe that can be stretched. In other words, capacitance increases with increasing injection pressure and increasing volume of fluid in the syringe. The total system capacitance is unique to each infusion system and depends on several factors in addition to the pressure and volume of fluid remaining in the system. Such factors include, but are not limited to, the construction of the injector, the mechanical properties of the materials used to construct the syringe, plunger, the pressure jacket surrounding the syringe and the fluid lines that infuse the fluid into the patient, the dimensions of the syringe, plunger and pressure jacket, the diameter of the tubing and other orifices through which the fluid must pass under pressure, and fluid properties such as temperature, viscosity and density.

[0056] In some infusion systems, such as infusion systems having two or more syringes each independently driven by a piston of a fluid injector, where two or more different fluids having different properties such as viscosity, temperature and / or density are stored separately in two or more syringes, the fluid flow rate may vary during an infusion procedure having multiple stages in which the infusion of a first fluid having a first property is followed by the infusion of a second fluid having a second property different from the first property. In such an infusion procedure, the overall fluid flow rate during the transition between the infusion of the first fluid and the infusion of the second fluid may vary or fluctuate due to differences in the reservoir pressures and fluid flow dynamics within the infusion system for the two fluids. For example, a more viscous fluid may require a higher applied pressure to achieve the same fluid flow rate as a less viscous fluid. Thus, a first infusion stage using a first fluid having a relatively high viscosity, such as contrast, may require a higher applied pressure to achieve a target flow rate than a second infusion stage using a second fluid having a relatively low viscosity compared to the first fluid, such as saline. In an injection having a first stage of injecting a first fluid followed by a second stage of injecting a second fluid, the pressure differential required to achieve target flow rates of the two different fluids may cause undesirable fluctuations in overall flow rate during the transition between the first and second stages.

[0057] In a closed system where the flow from at least one syringe can be blocked by a stopcock or other flow control member, there is no equalization of syringe capacitance between the syringes, and a capacitance can build up in the blocked syringe, which can affect the flow rate of the subsequent infusion from that syringe. In addition, the first fluid remaining in the fluid line must be pushed out of the line by the second fluid, which in certain circumstances may require a higher than desired pressure until the first fluid is purged. During the transition between infusion of the first fluid and infusion of the second fluid, the higher than desired pressure may result in an increased flow rate of the second fluid as the last of the first fluid exits the fluid line, especially during injections where the first fluid is more viscous than the second fluid. For example, as shown in FIG. 8, the dotted lines show the fluid flow rate variations observed when changing from a high viscosity fluid, such as contrast media, which can range from 2.0 to 30.0 cP (20° C.), to a low viscosity fluid, such as saline, which has a viscosity of 1.0 to 1.5 cP (20° C.), for several programmed desired flow rates. These undesirable variations in flow rate can, for example, result in differences in the respective fluid volumes, which can lead to inaccurate infusions of the respective fluid volumes, and can raise issues with the consistency of the respective bolus infusions and ultimately image quality when the contrast media is injected. Thus, there is a need in the art for improved control of infusions from a fluid injector. There is a further need for improved systems and methods that reduce fluid flow variations during infusions that involve at least one infusion change of fluids having different physical properties.

[0058] According to various embodiments, the present disclosure provides a method for providing a multi-stage fluid injection to a patient via a fluid injector, such as providing a fluid injection protocol using an imaging agent including a predetermined mixture of contrast and saline and a saline flush. The fluid injector may include two or more fluid reservoirs, such as reservoirs selected from the group consisting of a syringe, a compressible bag, a peristaltic pump, and various combinations thereof, such as at least one syringe and at least one peristaltic pump. In certain embodiments, the fluid injector may include a first syringe and a second syringe. In other embodiments, the fluid injector may include a first syringe, a second syringe, and a third syringe. In some embodiments, the syringe may be a rolling diaphragm syringe. The method may include injecting a first fluid for the fluid injection from at least a first fluid reservoir, the first fluid having a first viscosity and being infused to the patient at a first predetermined flow rate, the first predetermined flow rate may be a constant flow rate or may be an increasing flow rate. In some embodiments, the first fluid may be a contrast agent, saline, or a predetermined mixture of a contrast agent and saline. In certain embodiments, the first fluid may be a contrast agent, or a predetermined mixture of a contrast agent and saline.

[0059] The method may further include injecting at least an initial portion of the fluid infusion from at least a second fluid reservoir at a flow rate selected to minimize fluid flow fluctuations during the transition, as described herein. In this step, the second fluid has a second viscosity that is different from the first viscosity of the first fluid. In some embodiments, the first fluid may have a viscosity that exceeds the viscosity of the second fluid, for example when the first fluid is a contrast agent and the second fluid is saline. In other embodiments, the first fluid may have a viscosity that is less than the viscosity of the second fluid. In still other embodiments, the first fluid may have a viscosity that is approximately the same as the viscosity of the second fluid. The viscosity of the fluid may vary depending on the amount of dissolved solute per unit volume of solvent (i.e., a fluid with a higher concentration of dissolved solute will have a higher viscosity than a fluid with a lower concentration of dissolved solute). According to various embodiments of the present application, the first portion of the second fluid may be infused to the patient using a flow rate profile for a specified intermediate time interval that is different from the second preset flow rate, while the remaining volume of the second fluid (i.e., after the first portion) may be infused to the patient at the second preset flow rate. In various embodiments, the second preset flow rate is approximately the same as the first preset flow rate. As used herein, the term "approximately the same" when applied to a second value means having a range of -10% to 10% of the first value (i.e., having a range of 10% less than the first value to 10% more than the first value). In certain embodiments, the flow rate profile of the first portion of the second fluid includes a flow rate that is less than the first preset flow rate. For example, the flow rate of the first portion of the second fluid may be 0% to 100% of that of the second preset flow rate or 0% to 100% of that of the first preset flow rate.

[0060] In other embodiments, the flow rate of at least a first portion of the second fluid may be infused at a rate that varies over a specified intermediate time interval. For example, in one embodiment, the intermediate flow rate may vary by ramping from 0 mL / sec to a second preset flow rate over the specified intermediate time interval. In other embodiments, the intermediate flow rate may vary by ramping from 0 mL / sec to a transition flow rate over the specified intermediate time interval, the transition flow rate being less than at least one of the first preset flow rate and the second preset flow rate. According to other embodiments in which the intermediate flow rate includes ramping from 0 mL / sec to at least one of the first preset flow rate, the second preset flow rate, and the transition flow rate, the intermediate time may begin during the infusion of the first fluid at the first preset flow rate and continue past the end of the infusion of the first fluid and prior to the infusion of the second fluid at the second preset flow rate (i.e., the end of the specified intermediate time).

[0061] In other embodiments, the intermediate flow rate, i.e., the flow rate profile of the second fluid may be input by a system user based at least in part on one or more parameters selected from the group consisting of a table of infusion protocols, a first stage flow rate, a second stage flow rate, a transition flow rate, a catheter volume, a catheter diameter, a catheter length, a volume of a fluid line between the fluid reservoir and the patient, a fluid line diameter, a fluid line length, a temperature of the first fluid, a temperature of the second fluid, a viscosity of the first fluid, a viscosity of the second fluid, a programmed volume of the first fluid to be infused, and a programmed volume of the second fluid to be infused. For example, the intermediate flow rate may be manually input by a system user based at least in part on one or more predefined factors. Examples of predefined factors may be provided or derived from predefined tables of factors, such as one or more tables including one or more of a list of pressure, volume, flow rate, formulas, and any combination thereof. The tables may be viewed or utilized to determine or calculate the intermediate flow rate. In some embodiments, one or more tables may be recalled by a user from a processor memory and / or one or more tables may be displayed on a screen associated with the injector. In another embodiment, the table may be automatically recalled from memory by the injector processor to calculate intermediate flow rate suggestions based on various injection parameters. Other possible flow profiles for the first and / or second liquid stages are detailed in Figures 7A-7I.

[0062] In various embodiments, infusing at least an initial portion of the second fluid may include infusing at least an initial portion of the second fluid at an intermediate flow rate less than the second predefined flow rate for a specified intermediate time interval. In some embodiments, the specified intermediate time interval is selected to allow a remaining portion of the first fluid to pass through the fluid line and into the patient before commencing infusing the remaining portion of the second fluid, e.g., at the second predefined flow rate. The specified intermediate time interval may be based on one or more different factors. For example, the specified intermediate time interval may be selected based at least in part on characteristics of the fluid injector system configuration. For example, the fluid injector system configuration may include characteristics of the drive systems of the first pressurization feature and / or the second pressurization feature, such as motors, transmissions, and other mechanical characteristics of the first and / or second drive systems associated with the first pressurization feature and / or the second pressurization feature, respectively. Examples of such pressurization features include, but are not limited to, mechanical features of a motorized piston-based drive member that reversibly moves one or more plungers of one or more syringes, a motorized peristaltic pump-based drive system, and a clamshell compression feature for a compressible bag-based system. Pressurization of various mechanical components may compress the mechanical components to create an amount of slack where the force of the pressurization is not immediately converted to fluid flow due to compression and / or distortion of mechanical components such as the transmission and drive components of the fluid injector that apply the pressure. Other factors may include the capacitance of at least one of the system components, the capacitance of at least one of the first and second fluid reservoirs, the pressure and / or flow rate of the first fluid, the pressure and / or flow rate of the second fluid, the length of the fluid lines, the diameter of the fluid lines, the volume of the fluid lines, the length of the catheter, the diameter of the catheter, the volume of the catheter, and any combination thereof. Other factors may include expansion of fluid reservoirs, such as syringes and tubing, to the extent that an increase in the volume of fluid within the syringes and tubing beyond the desired volume selected to infuse during the injection procedure may occur due to an increase in system capacitance (i.e., an increase in fluid volume capacity).The total system capacitance is unique to each infusion system and depends on several factors in addition to the pressure and volume of fluid remaining in the system, including but not limited to fluid properties (viscosity, temperature, etc.), the construction of the injector, the mechanical properties of the materials used to construct the syringe or reservoir, the plunger, the pressure jacket around the syringe, the fluid lines through which the fluid is delivered to the patient, the dimensions of the syringe, the plunger, the pressure jacket, the diameter of the tubing or other orifices through which the fluid must pass under pressure, and fluid properties such as temperature, viscosity, and density. System capacitance can cause a discrepancy between the programmed volume of fluid delivered and the actual volume of fluid delivered. For example, at the start of a pressurized infusion, the initial pressure applied during the application of flow pressure can cause system components to expand and / or mechanical components to compress during the application of force, so that the corresponding volume of fluid is not delivered to the patient.

[0063] According to various embodiments, the first fluid may be a contrast agent, such as a CT contrast agent, a CV contrast agent, an MRI contrast agent, a PET radioactive contrast agent, an ultrasound contrast, or any combination thereof. In other embodiments, the first fluid may be a dual flow mixture of a contrast agent, as described herein, and a second fluid, such as saline or another flushing fluid, such as lactated Ringer's, in a first specified ratio. In still other embodiments, mixtures of three or more fluids are contemplated, including at least one contrast agent, saline, and a third medical fluid, such as a second contrast agent or other medical fluid, in specified ratios. According to various embodiments, the second fluid may be a medical flushing fluid, such as saline or water, or a mixture of a contrast agent and a flushing agent, the mixture having a second specified ratio of contrast agent and flushing agent that is different from the first specified ratio. According to some embodiments, the first specified ratio of contrast to flushing fluid and / or the second specified ratio of contrast to flushing fluid may vary over the course of the injection protocol. For example, in a dual flow contrast injection of a first fluid at a first specified ratio, the first fluid injected may begin at a ratio of 80:20 contrast to saline and increase to a ratio of 20:80 contrast to saline over at least a portion of the injection time of the first fluid. In another example, the second fluid may include a dual flow ramp-up at a second specified ratio. In this example, the second fluid injected may begin at a specified ratio of 10:90 contrast to saline and increase to a specified ratio of 0:100 contrast to saline over the remaining time of the injection of the second fluid. According to other embodiments, an initial portion of the second fluid may be injected as a specified dual flow ratio of the first and second fluids over a specified intermediate time. In yet other embodiments, an initial portion of the second fluid may be injected at a predetermined gradient from a specified intermediate dual flow ratio of the first fluid to the second fluid to a second specified intermediate dual flow ratio of the first fluid to the second fluid over a specified intermediate time period.One of ordinary skill in the art will understand upon reading this disclosure that the ratio of the first and second fluids used in the dual flow portion of the infusion may be any ratio of the first and second fluids, and the specific ratios detailed herein are for reference only. All other possible ratios are within the scope of the present invention. In other embodiments, the volume of the initial portion of the second fluid infusion may be determined by one or more of the volumetric capacity of the fluid line between the second fluid reservoir and the patient, the capacitance of at least one of the first and second fluid reservoirs, and the infusion system compliance.

[0064] According to various embodiments of the present application, the flow profile of the initial portion is selected to minimize deviations in flow rate over a specified intermediate time interval. For example, as shown in FIG. 8, a fluid transition from a first fluid having a different viscosity to a second fluid having a different viscosity may result in flow fluctuations or other deviations from the intended fluid flow rate over a specified intermediate time interval. For example, in some embodiments where the fluid flow transitions from a first fluid having a higher viscosity to a second fluid having a lower viscosity, flow fluctuations may be observed because the second fluid must be pressurized to a pressure that exceeds the pressure required to push the remaining first fluid out of the fluid pathway and into the patient at the first predetermined flow rate. The pressure of the second, less viscous fluid may increase as soon as the tail of the higher viscosity fluid exits the fluid pathway, causing rapid fluctuations in the fluid velocity of the second fluid exiting the fluid pathway. By appropriately selecting the flow rate of the initial portion of the second liquid, for example by selecting a flow rate that is less than the first predetermined flow rate and the second predetermined flow rate as shown herein, the sudden increase in liquid velocity of the second liquid exiting the liquid path may be reduced, minimized or substantially eliminated.

[0065] According to various embodiments, the flow rate and / or flow profile of the initial portion of the second fluid may be calculated using a formula that takes into account one or more of the various factors described herein to provide a calculated transition flow rate selected to minimize any fluctuations or deviations in the fluid flow rate of the fluid entering the patient during the transition from the first fluid to the second fluid. According to some embodiments, the flow rate and / or flow profile of the initial portion is based on Equation (1) below: Q(transition) = Q(program setting) - Q(adjusted) (1) According to equation (1), Q(Transition) is the desired flow rate profile across the transition between the first and at least the second fluid by adjusting the movement of the drive member (adjusting the speed over the distance) to control the fluid flow out of the catheter tip, Q(Programmed) is the desired flow rate profile of the at least the second fluid, and Q(Adjusted) is the adjustment of the flow rate of the second fluid required to result in a fluid flow rate from the catheter that is substantially similar to Q(Programmed) as a result of Q(Transition) at the transition between the first and at least the second fluid. According to certain embodiments, the intermediate time can be a consideration of the time it takes for the remaining volume of the first fluid to be infused from the fluid line, e.g., the time obtained by dividing the volume of the fluid line and catheter by the programmed flow rate. To avoid variations in fluid flow, values ​​of the equation are selected such that Q(Transition) results in a flow rate approximately similar to Q(Programmed).

[0066] According to another embodiment, the flow rate and / or flow profile of the initial portion is based on Equation (2) below: Q(t)=Q(p)-(C(1)-C(2)) / t(t) (2) According to equation (2), Q(t) is the intermediate flow rate, Q(p) is the second predetermined flow rate, C(1) is the steady state system compliance at the first fluid stage, C(2) is the system compliance during the second fluid infusion, and t(t) is the derived time to infuse a volume associated with the system compliance (C(2)). According to various embodiments, the system compliance during the first fluid infusion comprises a first compliance coefficient associated with one or more of the first fluid reservoir, the first infusion mechanism, and a set of tubing in operative fluid communication with the first fluid reservoir, and the system compliance during the second fluid infusion comprises a second compliance coefficient associated with one or more of the second fluid reservoir, the second infusion mechanism, and a set of tubing in operative fluid communication with the second fluid reservoir. The system compliance of the first reservoir and / or at least the second reservoir may be measured, for example, using a flow sensor in the fluid pathway between one or more reservoirs and the catheter. Alternatively, one or both of the system compliances of the first and / or at least the second reservoir may be predicted based on coefficients of the fluid infuser, the first or second fluid reservoir, and the first or second fluid, respectively. According to these embodiments, the system compliance during the first fluid infusion comprises a first compliance coefficient associated with one or more of the first fluid reservoir, the first infusion mechanism, and the tubing set and catheter in operative fluid communication with the first fluid reservoir, and the system compliance during the second fluid infusion comprises a second compliance coefficient associated with one or more of the second fluid reservoir, the second infusion mechanism, and the tubing set and catheter in operative fluid communication with the second fluid reservoir (including the pressure applied to each fluid reservoir and the volume of fluid remaining in each fluid reservoir). Alternatively, the capacitance of the fluid injector and associated components may be measured at least in part optically, for example by measuring the expansion of fluid reservoirs, compression of mechanical components and plunger features, and deflection of system components upon pressure comparison between relaxed and pressurized states.

[0067] As described herein, in certain embodiments of the fluid injector and methods, the first fluid reservoir may be a first syringe operably connected to a first drive member of the fluid injector, and the at least second fluid reservoir may be at least a second syringe operably connected to at least a second drive member of the fluid injector.

[0068] For example, according to some embodiments, a fluid injector system for providing a multi-stage fluid injection to a patient may include at least one first syringe and at least one second syringe. The at least one first syringe may be configured to receive a first fluid of the multi-stage fluid injection, the first fluid having a first viscosity, and the injector may include at least one first drive member operatively connected to the at least one first syringe, the at least one first drive member operable to dispense the first fluid of the multi-stage fluid injection. The at least one second syringe may be configured to receive a second fluid of the multi-stage fluid injection, the second fluid having a second viscosity different from the first viscosity, and the injector may include at least one second drive member operatively connected to the at least one second syringe, and the at least one second piston operable to dispense the second fluid of the multi-stage fluid injection. The injector may further include a fluid line fluidly connected to the at least one first syringe and the at least one second syringe and configured to infuse at least one of a first fluid of a multi-stage fluid infusion from the at least one first syringe to the patient and a second fluid of a multi-stage fluid infusion from the at least one second syringe to the patient. In various embodiments, the injector system may include a third syringe, and in other embodiments, other infusion mechanisms, such as one or more peristaltic pumps and / or one or more compressible reservoirs. According to various embodiments, the first syringe and the at least second syringe may be part of a closed system, in which the first syringe and the at least second syringe are configured to be individually isolated from the remainder of the fluid pathway, for example, by a valve, stopcock, or other structure that can selectively and reversibly isolate one or both of the first syringe and the at least second syringe from the fluid pathway. According to other embodiments, the first syringe and / or the at least second syringe may be part of an open system, where one or both of the first syringe and the at least second syringe are configured to be in fluid communication with a fluid pathway during an injection procedure.Various embodiments of the fluid injector may include a control device configured to control movement of a first drive member associated with at least one first syringe and movement of at least one second drive member associated with at least one second syringe to control infusion of a first fluid and a second fluid of a multi-stage fluid injection to a patient. For example, the control device may be configured to control the first drive member to inject the first fluid at a first predetermined flow rate, control the at least one second drive member to inject an initial portion of at least a second fluid of the fluid injection from the at least one second syringe at an intermediate flow rate profile for a specified intermediate time that is different from the second predetermined flow rate, and inject a remaining portion of the second fluid at least corresponding to the second predetermined flow rate, the second fluid having a second viscosity that is different from the first viscosity. According to various embodiments, a control device, such as a processor, may be configured to operate the fluid injector to individually open and close fluid connections between the first and / or second syringes and the remaining portions of the fluid pathway.

[0069] With reference to FIG. 1, a fluid injector 10, such as an automatic or powered fluid injector (hereinafter referred to as "injector 10"), is configured to connect to and actuate one or more syringes 12 (hereinafter referred to as "syringes 12") that may be filled with a fluid F, such as a contrast agent, saline solution, or any desired medical fluid. The injector 10 may be used during a medical procedure to inject medical fluid into a patient's body by actuating a plunger 14 of each syringe 12 with a drive member, such as a piston 19 (shown in FIG. 2), such as a linear actuator or piston element. The injector 10 may be a multi-syringe injector having two, three, four or more syringes, and the several syringes 12 may be oriented in parallel or in other relationships and actuated separately by respective drive members / pistons 19 associated with the injector 10. For example, in an embodiment using two or more syringes arranged in parallel or other relationship and filled with two different fluids, the injector 10 may be configured to infuse fluid from one or both of the syringes 12, either sequentially or simultaneously. According to one embodiment, the fluid injector 10 may be a dual head injector having two syringes 12a and 12b, a first syringe 12a for infusing a contrast agent or other medical fluid, and a second syringe 12b for infusing saline or other medically acceptable flushing agent to flush the contrast agent toward the patient. In another embodiment, the fluid injector 10 may have three syringes 12, a first and second syringe for infusing one or two different contrast agents or other medical fluids, and a third syringe for infusing saline or other medically acceptable flushing agent to flush the contrast agent toward the patient. According to various embodiments, the fluid injector 10 may be configured to infuse contrast and saline separately (e.g., infusing a specific volume of saline for a specific period of time, followed by a specific volume of contrast for a specific period of time, and then infusing a second volume of saline for a specified period of time to flush the contrast agent through the tubing and into the patient).According to various embodiments, the fluid injector 10 may be configured to infuse contrast and saline separately or as a mixture (e.g., infusing a specific volume of saline for a specific time period followed by a specific volume of contrast or a specific ratio of contrast and saline (i.e., a "dual flow" process) for a specific time period, followed by a second volume of saline for a specific time period to flush the contrast through the tubing and into the patient). A specific injection protocol may be programmed into the injector by a technician (or a pre-written protocol may be used) to infuse desired volumes of saline, contrast, a specific ratio of contrast and saline mixture, etc., at desired flow rates, durations, and volumes for each solution. The fluid injector 10 may have at least one bulk fluid source (not shown) for filling the syringes 12a,b, and in some embodiments the fluid injector 10 may have multiple bulk fluid sources, one for each of multiple syringes, to fill each of the multiple syringes with the desired fluid.

[0070] A fluid pathway set 17 is in fluid communication with each syringe 12, thereby placing each syringe in fluid communication with a catheter (not shown) for infusing fluid F from each syringe 12 to a catheter inserted into a vascular access site of a patient. In some embodiments, the flow of fluid from one or more syringes 12 may be regulated by a fluid control module (not shown) that manipulates various valves, stopcocks, and flow regulation configurations to regulate the infusion of saline and contrast to the patient based on user-selected injection parameters such as injection rate, duration, total injection volume, and ratios of fluids exiting the syringes 12 (including specific ratios of each fluid for a dual flow injection protocol).

[0071] With reference to FIG. 2, a drive member 19, such as a reciprocating drive piston, driven by a motor 31 may be configured to extend from and enter each syringe port 13 through an opening in the front end of the injector housing. In an embodiment of a liquid injector having multiple syringes, a separate drive member / piston 19 may be provided for each syringe 12. Each drive member / piston 19 is configured to apply power to at least a portion of a syringe 12, such as a plunger 14 or the distal end of a rolling diaphragm syringe (e.g., as described in PCT / US2017 / 056747, U.S. Patent No. 5,333,363, and U.S. Patent No. 5,333,363, the disclosures of which are incorporated herein by reference). The drive member or piston 19 may be reciprocally operable via an electromechanical drive component, such as a ball screw shaft, a voice coil actuator, a rack and pinion gear drive, a linear motor, a linear actuator, or the like, driven by a motor 31. The motor 31 may be an electric motor.

[0072] Examples of suitable preloaded fluid injectors 10 are disclosed in U.S. Patent Nos. 5,393, 6,433, 6,511, 6,623, 6,711, 6,893, 7,946, 7,103, 7,133, 7,146, 7,152, 7,162, 7,213, 7,222, 7,25

[0073] Having described the general structure and function of a particular embodiment of the fluid injector 10, an embodiment of a syringe 12 configured for use with the injector 10 will now be described with reference to FIG. 2. Generally speaking, the syringe 12 has a cylindrical syringe barrel 18 formed from glass, metal, or a suitable medical grade plastic. The barrel 18 has a proximal end 20 and a distal end 24 with a sidewall 119 extending therebetween along the length of a longitudinal axis 15 that extends through the center of the barrel 18. In some examples, the distal end 24 may have a conical shape that tapers distally from the cylindrical barrel 18. A nozzle 22 extends from the distal end 24. The barrel 18 has an exterior surface 21 and an interior surface 23 and defines an interior volume 25 for receiving fluid. The proximal end 20 of the barrel 18 may be sealed with a plunger 14 that is reciprocatable through the barrel 18 by reciprocating motion of a corresponding piston 19 or drive member. As the plunger 14 advances through the barrel 18 , the plunger 14 is forced against the inner surface 23 of the barrel 18 to form a fluid-tight seal.

[0074] 2, the proximal end 20 of the syringe 12 is sized and configured to be removably inserted into the syringe port 13 (shown in FIG. 1) of the injector 10. In some examples, the proximal end 20 of the syringe 12 forms an insert 30 that is configured to be removably inserted into the syringe port 13 of the injector 10, while the remainder of the syringe 12 remains outside of the syringe port 13.

[0075] Syringe 12 may be made of any suitable medical grade plastic or polymeric material, preferably a transparent or substantially translucent plastic material. The material of syringe 12 is desirably selected to meet the necessary tensile and plane stress requirements, water vapor permeability, and chemical / biological compatibility. Exemplary syringes suitable for use with injector 10 shown in FIG. 1 are described in U.S. Patent Nos. 5,393, 6,433, 6,511, 6,711, 6,893, 7,943, 7,996, 8,103, 9,112, and 9,123, the disclosures of all of which are incorporated by reference in their entirety.

[0076] In some examples, such as that shown in Figure 3, the injector 10 may be configured to receive and retain a pressure jacket 32 ​​in each syringe port 13 of the injector 10. Although Figures 1 and 3 depict the fluid injector 10 with two syringe ports 13, and for the injector 10 shown in Figure 3, each syringe port 13 has a corresponding pressure jacket 32, other examples of the fluid injector 10 may include a single syringe port 13 and optionally a corresponding pressure jacket 32, or may include more than two syringe ports 13 with a corresponding number of optional pressure jackets 32. In embodiments with a pressure jacket, each pressure jacket 32 ​​may be configured to receive a syringe, such as a syringe for angiography (CV) procedures or a rolling diaphragm syringe 34 (suitable examples of which are described in PCT / US2017 / 056747, US Patent No. 5,333,626, and US Patent No. 5,333,626). A fluid path set similar to fluid path set 17 shown in FIG. 1 may be fluidly connected to the discharge end of each rolling diaphragm syringe 34 for infusing fluid from the syringe 34 through tubing that is connected to a catheter, needle, or other infusion connection (not shown) inserted into a vascular access site of the patient. According to various embodiments, the syringe 12 or 34 may be a pre-filled syringe, i.e., the syringe may be pre-filled with a medical fluid, such as contrast media or saline, as provided by the syringe manufacturer. According to some embodiments, the discharge end of the pre-filled syringe may need to be pierced or otherwise punctured with a sharp object prior to the injection procedure to allow fluid to be expelled from the syringe into a fluid line leading to the patient, as described herein.

[0077] 4, generally speaking, the rolling diaphragm syringe 34 includes a hollow body 36 defining an interior volume 38. The body 36 has a forward or distal end 40, a rearward or proximal end 42, and a flexible sidewall 44 extending therebetween. The proximal end 42 may be configured to act as a piston to pressurize the interior of the syringe to draw fluid into and expel fluid from the interior of the syringe, as described herein. The sidewall 44 of the rolling diaphragm syringe 34 forms a flexible, pliable or flexible, yet self-supporting body that is configured to evert up upon itself as a "rolling diaphragm" under the action of a drive member or piston of the fluid injector 10. The drive member / piston 19 may be configured to releasably engage a drive member engagement portion 52 at the proximal end 42 of the rolling diaphragm syringe 34 (examples of which are described in PCT / US2017 / 056747). In operation, side wall 44 is configured to be flipped such that the outer surface of side wall 44 folds radially inward when drive member / piston 19 moves proximal end 42 distally, and to unfold radially outward in the opposite manner when drive member / piston 19 retracts proximal end 42 proximally.

[0078] 4, a rearward or proximal portion of sidewall 44 is connected to a closed end wall 46, and a forward or distal portion of sidewall 44 forms a discharge neck 48 opposite closed end wall 46. Closed end wall 46 may have a concave shape to facilitate initiation of eversion or everting of sidewall 44, to increase the mechanical strength of closed end wall 46, and / or to provide a receiving recess for receiving a distal end of drive member / piston 19. For example, closed end wall 46 may form a receiving end recess that connects directly to a similarly shaped distal end of drive member / piston 19. In some examples, at least a portion of drive member / piston 19 may be molded to generally match the shape of closed end wall 46, or alternatively, end wall 46 may conform to generally match the shape of at least a portion of drive member / piston 19 under pressure from drive member / piston 19 as drive member / piston 19 moves distally.

[0079] The end wall 46 may have a central portion 50 having a generally dome-shaped configuration and a drive member engagement portion 52 extending proximally from the central portion 50. The drive member engagement portion 52 is configured to releasably interact with a corresponding engagement feature on the drive member / piston 19 of the injector 10, for example, when the drive member / piston is retracted. The rolling diaphragm syringe 34 may be made of any suitable medical grade plastic or polymeric material, preferably a transparent or substantially translucent plastic material. The material of the rolling diaphragm syringe 34 is preferably selected to meet the necessary tensile and plane stress requirements, water vapor permeability, and chemical / biological compatibility.

[0080] Referring to FIG. 5, a fluid injector 10 according to another example of the present disclosure is shown. The injector 10 has a housing 54 that houses various mechanical drive components, electrical and power components necessary to drive the mechanical drive components, and control components such as electronic memory and electronic control devices used to control the operation of a reciprocable piston (not shown). The fluid injector 10 further has a multi-patient disposable system (MUDS) 56 that is removably connectable to the fluid injector 10. The MUDS 56 has one or more syringes and / or pumps 58. In some embodiments, the number of syringes 58 corresponds to the number of pistons in the fluid injector 10. In some examples, as shown in FIG. 6, the MUDS 56 has three syringes 58a-58c arranged in parallel. Each syringe 58a-58c has a bulk fluid connector 60 for connection to a respective bulk fluid source (not shown) via a MUDS fluid pathway 62. The MUDS fluid pathway 62 may be formed as a flexible tube with a piercing element at the end of the flexible tube that is connected to the bulk fluid connector 60. The injector 10 and corresponding MUDS 56 shown in Figure 5 are described in detail in U.S. Patent No. 5,399,992, the disclosure of which is incorporated herein by reference.

[0081] The MUDS 56 may include one or more syringes and / or pumps 58a-58c. In some embodiments, the number of syringes 58 corresponds to the number of drive members / pistons of the fluid injector 10. In some examples, such as shown in Figures 5 and 6, the MUDS 56 includes three syringes 58a-58c arranged in a parallel configuration. Each syringe 58a-58c includes a bulk fluid connector 60 for connection to a respective bulk fluid source (not shown) via a MUDS fluid pathway 62. The MUDS fluid pathway 62 may be formed as a flexible tube connected to the bulk fluid connector 60, which may terminate in a piercing element.

[0082] 6, the MUDS 56 includes a frame 64 supporting one or more syringes 58a-58c. The syringes 58a-58c may be removably or non-removably connected to the frame 64. Each syringe 58a-58c has an elongated, generally cylindrical syringe body. Each syringe 58a-58c has a fill port 66 in fluid communication with the MUDS fluid pathway 62 for filling the syringes 58a-58c with fluid from a bulk fluid source. Each syringe 58a-58c further includes a discharge outlet or discharge tube 68 at a distal end terminal portion thereof. The discharge outlet 68 of each syringe 58a-58c is in fluid communication with a manifold 70. Associated with each discharge outlet 68 is a valve 72 operable between a fill position in which the fill port 66 is in fluid communication with the interior of the syringe while the discharge outlet 68 is fluidly isolated from the interior of the syringe, and an infusion position in which the discharge outlet 68 is in fluid communication with the interior of the syringe while the fill port 66 is fluidly isolated from the interior of the syringe. The manifold 70 has a fluid passage in fluid communication with each syringe 58a-58c and in fluid communication with a fluid outlet line 74 which is in fluid communication with a port 76 configured to be connected to an as-needed fluid pathway element (not shown) for infusing the fluid to a patient.

[0083] In various embodiments of the injector 10, such as any of the injectors shown in Figures 1, 3 and 5, a motor 31 (Figure 2) generates power to reciprocate the drive member / piston 19 distally to expel fluid from the syringe 12, 34 or MUDS 56. The motor 31 may have drive components, such as gears and shafts, operatively connected to the drive member / piston 19 to reciprocate the drive member / piston 19. Each motor 31 must be calibrated to correlate its operating characteristics, such as input current and output torque, to its associated flow rate, pressure and tolerances. As shown herein, calibration may be desirable to compensate for variations or out-of-specification behavior from any of the various components of the injector 10, such as any variations in motor performance characteristics in an injector having two or more syringes driven by two or more motors. For example, the conversion of motor input torque to injector output pressure for one motor 31 may differ from another motor 31. This variation may be exacerbated by variations in the tolerances of the drive train of the injector 10. The flow rate and pressure accuracy of the injector 10 is directly related to the system and method used to calibrate the motor 31 .

[0084] According to one example of the present disclosure, the liquid injector 10 described above with reference to FIGS. 1-6 may be configured to perform a multi-stage liquid injection including injecting a first liquid F1 in a first stage followed by injecting a second liquid F2 in a second stage. In the first stage, the first liquid F1 is injected from at least a first syringe, e.g., syringe 12a of FIG. 1 or one of syringes 58b and / or 58c of FIGS. 5-6. In the second stage, the second liquid F2 is injected from at least a second syringe, e.g., syringe 12b of FIG. 1 or syringe 58a of FIGS. 5-6. The first and second syringes will be described below with reference to FIGS. 5-6. They will therefore be referred to as the first syringe 58b and the second syringe 58a. However, it is understood that the systems and methods described herein are equally applicable to syringes 12a-12b of FIG. 1, an injector having two or more rolling diaphragm syringes 34 as shown in FIGS. 3-4, or any other set having a minimum number of two syringes in a liquid injection system.

[0085] The first fluid F1 in the first syringe 58b and the second fluid F2 in the second syringe 58a may be different fluids, such as medical fluids having different properties, such as different viscosities. Alternatively, the first fluid F1 and the second fluid F2 may be the same fluid, e.g., the same medical fluid, but with different concentrations or temperatures, or may be the same fluid infused at different flow rates. For example, the first and second fluids F1, F2 may have one or more of different viscosities, temperatures, and / or densities. In one example of the present disclosure, the first fluid F1 may be a contrast agent, as described herein, having a first viscosity, and the second fluid F2 may be saline, having a second viscosity, typically lower than the first viscosity. In some embodiments, the fluid injector may have a third syringe 58c containing a third fluid F3, which may be the same or different from the first fluid F1 and the second fluid F2. For example, F3 may be a contrast agent, which may be the same as the first liquid F1, F3 may be a different contrast agent than F1, or F3 may be the same contrast type as F1 but of a different concentration. In a first stage of the multi-stage injection, the first liquid F1, i.e., contrast, may be injected from the first syringe 58b at a first preset flow rate programmed into the injector 10. The infusion of the first liquid F1 at the first preset flow rate is achieved by applying pressure to the first liquid F1 in the first syringe 58b, such as by driving the plunger of the first syringe 58b with the piston 19. In this case, the applied pressure required to achieve the desired first preset flow rate is a function of the first viscosity of the first liquid F1. Because the viscosity of the contrast of the first liquid F1 is generally high, a higher applied pressure is generally required to achieve the preset flow rate compared to the applied pressure required to achieve the same flow rate for a liquid having a lower viscosity, such as saline. Following the first stage of the multi-stage injection, the second stage includes the injection of a second fluid F2, i.e., saline, from the second syringe 58a. The second predetermined flow rate of the second fluid F2 may be the same as, greater than, or less than the first predetermined flow rate of the first fluid F1.In a liquid injection in which the first and second preset flow rates are to be the same, the pressure required to infuse the second liquid F2 may differ from the pressure required to infuse the first liquid F1 due to the difference between the first viscosity of the first liquid F1 and the second viscosity of the second liquid F2. In this example, the pressure applied to the first liquid F1, i.e., the contrast agent, is generally higher than the pressure applied to the second liquid F2, i.e., the saline solution, to achieve the same flow rate. In another example, the second preset flow rate of the second liquid F2 may be different from the first preset flow rate of the first liquid F1, but in this case too, the pressure required to achieve the preset flow rate of the first liquid F1 and the preset flow rate of the second liquid F2 will be different.

[0086] If the pressure required to achieve the second predetermined flow rate of the second fluid F2 in the second stage is applied regardless of the predetermined flow rates of the first and second fluids F1 and F2, the difference in pressure applied between the first and second stages of the multi-stage injection may cause undesirable variations in the actual flow rate at the catheter tip of the fluid path set 17. In particular, during the initial portion of the second stage, the first fluid F1 remaining in the fluid path set 17 may be pushed or purged from the infusion system by the second fluid F2. Because the remaining high viscosity first fluid F1 remains in the fluid path set 17, the high pressure may cause the second syringe 58b to inject the less viscous second fluid F2 while the remaining first fluid is being injected. However, after substantially all of the remaining first fluid has exited the fluid path set 17, the pressure exerted on the less viscous second fluid F2 may be high, resulting in undesirable variations in the flow rate of the second fluid F2 as it exits the catheter. The present disclosure provides a method for minimizing the effects of fluid migration as described herein. Additionally, in an open infusion system, such as the fluid injector 10 described herein with reference to Figures 1-2, in which the first and second syringes 12a, 12b are in fluid communication for multi-stage injection, equalization of the capacitance of the first and second syringes 12a, 12b may contribute to undesirable variations in the actual flow rate.

[0087] In an embodiment, in order to mitigate undesirable fluctuations in the actual flow rate and to more accurately match the actual flow rate to the preset flow rate, the first part of the second stage may be a transition stage in which the pressure applied to the second liquid F2 in the second syringe 58a is reduced while remaining first liquid F1 is purged from the infusion system.

[0088] The transition stage of the multi-stage injection is performed by an electronic control device responsible for controlling the movement of the piston 19 in the second syringe 58a to dispense the second fluid F2 from the second syringe 58a. The movement of the piston 19 is controlled via the actuation of a motor, such as the motor 31 shown in FIG. 2, which is responsible for moving the piston 19 in the second syringe 58a to apply pressure to the second fluid F2. FIGS. 7A-7I show various embodiments that do not impose flow rate profile limitations for injecting the first and second fluids in the first stage during the transition stage and the remaining stages that utilize methods described herein to reduce fluid fluctuations during the transition stage. As shown in FIG. 7A, according to various examples of the present disclosure, the electronic control device operates the motor 31 at a speed to inject the first fluid F1 from the first syringe 12a and / or the first syringe 58b in the first stage at a first preset flow rate, for example, programmed into the injector 10. After the first stage injection is completed, the electronic control device operates the motor 31 at a lower speed during a transition stage, i.e., the first part of the second stage (which reduces the pressure at which the second fluid F2 is infused), to inject the second fluid F2 from the second syringe 12b and / or the second syringe 58a into the patient at a rate lower than the second preset flow rate for the second stage. After this transition stage is completed, the electronic control device may operate the motor 31 at a speed to inject the remainder of the second fluid F2 at the second preset flow rate to complete the multi-stage injection. With reference to FIG. 7B, the transition stage comprises a long ramp in which the injection of the second fluid rises from zero flow rate (zero piston speed), begins approximately simultaneously with the first stage injection of the first fluid, and rises to a piston speed sufficient to achieve the second preset flow rate after the first stage injection is completed. With reference to Figure 7C, a flow profile shows a long cross-slope transition phase injection protocol in which the motor speed of the first fluid phase ramps down to zero while the motor speed of the second fluid in the transition phase ramps up to a second predefined flow rate. With reference to Figure 7D, a transition phase is shown having an ascending transition phase that begins approximately when the motor speed of the first phase ramps down to zero.7E and 7F show a transition phase with a programmed motor speed that starts at a second predefined flow rate for a short period of time, includes an optimal downward ramp when it is calculated that the second fluid has reached the end of the catheter, followed by a ramp back to the second predefined phase after it is calculated or presumed that the delivery of the first fluid flow is complete. In FIG. 7E, the transition phase ramp to the second predefined flow rate begins before the end of the first phase, while FIG. 7F shows an embodiment in which the transition phase ramp to the second predefined flow rate begins after the injection of the first phase. With reference to FIG. 7G, a stepwise increase in the speed and flow rate of the second fluid motor during the transition phase is shown. The stepwise increase in motor speed may increase until the second predefined flow rate is reached. With reference to FIG. 7H, the motor speed of the first fluid stage drive member is reduced to an intermediate speed during the transition phase, and when the first motor speed reaches approximately zero, the motor speed of the second fluid stage drive member is increased to an intermediate speed during the transition phase before increasing to a speed associated with the second predefined flow rate. Figure 7I includes intermediate velocities during the transition phase of both the first and second fluid phases, similar to Figure 7H, and overlaps the timing of the ramp down and ramp up of the first and second injector motors, respectively, during the transition phase. The duration of the injection of the transition phase may be determined, for example, by calculating the time required to flush the remaining volume of the first fluid F1 from the fluid path set. Often, this volume may be calculated as the fluid volume of the fluid path set.

[0089] According to a particular example of the present disclosure, the electronic control device is programmed to set the transition stage reduced flow rate according to the following equation (2): Q(t)=Q(p)-(C(1)-C(2)) / t(t) (2) In Equation 2, Q(t) is the reduced flow rate of the multi-stage fluid infusion during the transition stage. Q(p) is the second predefined flow rate for the infusion during the second stage. C(1) is the steady-state system capacitance (compliance) of the first stage determined during the infusion of the first stage. C(2) is the system capacitance (compliance) of the second stage. t(t) is the derived time to infuse a volume related to the system compliance (C(2)). In some examples, C(2) and / or t(t) may be obtained from a look-up table or derived from an equation. In other examples, C(2) and t(t) may be obtained or derived in real time using the injector 10.

[0090] The method implemented through the implementation of equation (2) to calculate the reduced flow rate Q(t) in the transition stage utilizes knowledge of the system capacitances of the different stages (C(1) and C(2)) along with the transition time t(t) and also utilizes the programmed flow rate Q(p) of the low viscosity second stage, i.e. the default flow rate. Inputs include the real-time pressure (P1) of the first fluid F1 in the first stage, the derived pressure (P2) of the second fluid F2 in the second stage, the derived transition time t(t) of the transition stage, and the injected volume in the second stage (X2).

[0091] The pressure of the second stage (P2) and the transition time t(t) of the transition stage may be derived according to the step diagram of Fig. 9. In particular, a first predefined flow rate of the first liquid F1, in this example the contrast agent, is used to determine how to calculate the transition stage flow rate Q(t). If the first predefined flow rate of the first liquid F1 is below a threshold value, in this example 5 mL / s, the transition stage flow rate Q(t) is calculated by measuring the steady state pressure during injection of the first liquid F1, approximating the catheter gauge, and estimating the steady state pressure of the second liquid F2 using the approximation of the catheter gauge. In particular, the estimated steady state pressure of the second liquid F2 may be derived from a table or other calculation based on the measured steady state pressure of the first liquid F1, as illustrated by the non-limiting exemplary look-up table shown in Fig. 10, which provides values ​​for system characteristics such as flow rate, contrast pressure, saline pressure, catheter size, etc. Using the steady state pressure of the first liquid F1 and the estimated steady state pressure of the second liquid F2, respectively, the system capacitances C(1) and C(2) in the first and second stages may be calculated as described below, with particular reference to Figure 12. The transition stage flow rate Q(t) may then be calculated from equation (2).

[0092] If the predefined flow rate of the first liquid F1 exceeds a threshold value, in this example 5 mL / s, the transition stage flow rate Q(t) is calculated by assuming a gauge value of the catheter, calculating an estimated steady-state pressure of the second liquid F2, and calculating the capacitance of the system at the second stage C(2). The estimated steady-state pressure of the second liquid F2 may be derived from an equation, such as the non-limiting exemplary equation shown in FIG. 11, which shows the pressure of the second liquid F2 as a function of flow rate for a known catheter size. The system capacitance C(2) at the second stage may be calculated as described below with particular reference to FIG. 12. The transition stage flow rate Q(t) may then be calculated from equation (2).

[0093] The timing of the transition phase is set to infuse the volume required to fill the fluid path set 17. In some instances, this volume may be between 5 mL and 20 mL depending on the inner diameter and length of the tubing. For example, for the second fluid F2 at the start of the second phase at reduced flow rate, it may be approximately 12 mL. This allows the first fluid F1 remaining in the fluid path set to be pushed through the fluid path set 17 and the catheter at a low flow rate and out of the fluid path set 17 and the catheter without undesirable fluctuations in the actual flow rate at the catheter. After the transition phase is completed, the second phase infusion of fluid F returns to the second phase programmed default flow rate Q(p) to infuse the remaining volume of the second phase programmed by the surgeon.

[0094] Equation (2) may be utilized by following the steps below: (1) Measure P1 during the first stage. This pressure should be measured either at steady state or at a predefined time period before transitioning to the second stage. (2) Derive P2 from a table or equation using the parameters of the second stage as input (i.e., the second fluid F2 being used, the predefined flow rate for the second stage, catheter gauge, etc.). (3) Derive the volume from the capacitance during the first stage by inserting P1 and X2 into the capacitance equation described herein. (4) Derive the volume from the capacitance during the second stage by inserting P2 and X2 into the capacitance equation. (5) Execute equation (1) to determine the reduced flow rate for the transition stage Q(t). (6) Modify the protocol to perform the transition stage at the reduced flow rate Q(t) for the volume required to fill the fluid path set 17, and return to the predefined flow rate Q(p) after completion of the transition stage.

[0095] According to some embodiments, the capacitance equation may be illustrated graphically in Figure 12. From the capacitance characteristic of one typical infuser, the infusion deficit is obtained according to equation (3) below.

[0096]

number

[0097] where z is the volume of fluid deficit (which may be measured in any suitable volume units, such as milliliters (mL)), y is the pressure (which may be measured in any suitable pressure units, such as pounds per square inch (psi)), x is the volume of fluid in the at least one syringe at the time of injection, and a, b, and c are constants for the particular surface. For example, for the surface shown in FIG. 12, a=0.097795815, b=-0.014798654, and c=11.030418. Once the volume of fluid deficit has been determined in this manner, the fluid infused to the patient can be correctively increased by an appropriate amount to compensate for the volume lost due to the capacitance and impedance of the fluid injector and / or the fluid. The piston can be overdriven by the fluid injector a calculated distance to infuse the predicted volume of fluid deficit (i.e., z) to ensure an accurate injection dose of fluid to the patient. The value "z" may be referred to as the "correction volume." Substituting P1 and X1 for y and x, respectively, in equation (3) gives the corrected volume of the first stage, which is substituted into (C1) in equation (2). Substituting P2 and X2 for y and x, respectively, in equation (3) gives the corrected volume of the second stage, which is substituted into (C2) in equation (2).

[0098] FIG. 8 is a graph showing the effect of utilizing the transition steps described above on the measured flow rate at the patient catheter end of the fluid pathway set 17 during the transition between the first and second stages of a multi-stage fluid infusion. The dashed lines represent various baseline infusion flow rates where no transition steps were implemented. The results show a significant increase in measured flow rate at the catheter end of the fluid pathway set 17 during the transition from the first stage to the second stage, which correlates with the rise in fluid pressure at the catheter. The solid line represents the same flow rate as the dashed line, but includes a transition step according to an embodiment of the present application at the beginning of the second stage of the multi-stage infusion. As can be seen by comparison with the corresponding dashed and dotted lines, the implementation of the transition step significantly reduces the variability in the measured flow rate at the catheter end of the fluid pathway set 17.

[0099] FIG. 13 illustrates the overall workflow of an injection protocol including a transition phase according to various embodiments of the present disclosure. As shown in FIG. 13, step 1310 includes inputting a desired flow profile for the injection, including a first predefined flow rate for the first fluid and, in some embodiments, a second predefined flow rate for the second fluid. The injection is started (1320), and in step 1330, the injector determines whether the first injectate phase will be followed by a subsequent second injectate phase. If the injector processor determines that the first injectate phase will not be followed by a second fluid phase, the injector completes injection of the first phase (1340) and then terminates the injection (1350). If the injector processor instead determines that the first injectate phase is scheduled to be followed by a second fluid phase, the injector evaluates (1360) the compliance of the currently injected first fluid phase and predicts (1370) the compliance of the subsequent second fluid phase based on the evaluation. For example, based on various system components associated with the second fluid reservoir and the characteristics of the first and second fluids. Once compliance is predicted, the fluid injector processor calculates (1380) an appropriate adjustment to the flow rate of the first portion of the second fluid stage injection and determines whether to inject a flow rate adjustment used to change the flow rate of the first portion of the second fluid stage. The injector then adjusts (1390) the flow profile of the first portion of the second fluid stage to the calculated value and injects the first portion of the second fluid at the calculated flow rate during the intermediate specified period. A feedback loop may then be performed in which the injector processor returns to step 1320 and begins injection of the second fluid stage at the second predefined flow rate after the injection of the first portion of the second fluid over the transition phase is completed. As the protocol continues, the injector determines whether to inject any additional phases (i.e., a subsequent contrast phase, a dual flow phase, or a saline phase) or whether the injection protocol can be completed after injection of the second phase.

[0100] FIG. 14 illustrates a workflow of an injection protocol including a transition stage for a particular embodiment of the disclosure, such as the injector shown in FIG. 5. As shown in FIG. 14, in step 1410, a first injection stage is initiated in which a first fluid is injected at a first predefined pressure. The injector may measure the pressure of the first fluid during the first stage in step 1415 and calculate (1440) the compliance of the first stage. The injector processor may approximate (1420) the pressure of the second fluid based on the measured pressure of the first fluid stage. For example, a data lookup table such as that shown in FIG. 11 may be consulted to approximate the pressure of the second fluid to provide the transition stage flow rate and the second predefined flow rate at which the second fluid is injected. Alternatively, the injector processor may calculate (1420) the pressure of the second fluid to provide the transition stage flow rate and the second predefined flow rate using the process shown in FIG. 9 with appropriate equations and surface plots. After approximating the second pressure, this value may be used by the injector along with detailed information about the capacitance characteristics of the injector's second fluid reservoir, fluid path, and second drive mechanism, as well as the characteristics of the second fluid, to calculate 1425 the compliance of the second fluid stage. The injector processor may then determine whether the compliance of the second fluid stage exceeds the compliance of the first fluid stage, step 1430. If the compliance of the second fluid stage exceeds the compliance of the first fluid stage, the injector determines 1435 that no flow rate adjustment is required for the initial portion of the second stage, and begins injection of the second fluid stage at the second default flow rate. Alternatively, if the calculation of the compliance of the second fluid stage indicates a significant difference between the compliance of the second fluid stage and the compliance of the first fluid stage (1455), a delta between the compliance values ​​may be determined and used to determine an intermediate flow rate for the first portion of the second fluid stage based on the difference (1460), determine an intermediate specified period or injection volume required to remove the first fluid from the fluid path / catheter, begin infusion of the second fluid at the intermediate corrected flow rate (1465) and infuse at the intermediate flow rate for the intermediate specified period, and increase the flow rate of the second fluid to a second default flow rate after completion of the volumetric infusion over the intermediate specified period (1470).

[0101] According to another embodiment of the workflow shown in Fig. 14, after step 1415 of measuring the pressure of the first liquid stage is performed, the pressure value may be used by the injector together with detailed information about the capacitance characteristics of the injector's first liquid reservoir, liquid path, and first drive mechanism, as well as the characteristics of the first liquid, to calculate 1440 the compliance of the first liquid stage. The calculated compliance of the first liquid stage may be used directly to provide a guide to the approximation 1420 of the pressure during the second liquid stage, and / or may be used to determine the flow rate 1445 of the first liquid stage, for example to ensure that this value is approximately equal to the expected first predetermined flow rate. In another embodiment, the calculated compliance value 1450 of the second liquid stage may be provided to step 1455, and this value may be provided to step 1455 together with the calculated compliance value 1440 of the first liquid stage to determine the delta or difference between the calculated compliances of the first and second liquid stages. The described workflow is exemplary and non-limiting, as other workflows exist within the scope of this disclosure that provide values ​​for the first and second fluid flow rates, the initial flow rate of the second fluid, the intermediate specified period for the initial flow rate of the second fluid, the compliance associated with the injection of the first fluid, the compliance associated with the injection of the second fluid, and other values ​​necessary to provide an injection protocol having fluid transition portions that do not include any significant variation throughout the fluid flows.

[0102] As described above, after the transition phase is completed, infusion of the remainder of the second phase is resumed at the second preset flow rate of the second fluid. According to an alternative embodiment of the present disclosure, the remainder of the second phase is infused at a flow rate faster than the preset flow rate to compensate for the effect of the slow transition phase on the total infusion time of infusing both phases into the patient.

[0103] While the present disclosure has been described in detail for illustrative purposes based on what are currently considered to be the most easily operable and preferred embodiments, it is to be understood that such details are for such purposes only, and that the present disclosure is not limited to the disclosed embodiments, but is intended to cover modifications and equivalent arrangements beyond. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment. [Explanation of symbols]

[0104] 10 Front-loading liquid syringe, injection body 12 Syringe 12a First Syringe 12b Second Syringe 13 Syringe port 14 Plunger 15 Longitudinal axis 17 Liquid Path Set 18 Cylindrical Syringe Barrel, Cylindrical Barrel 19 Piston, driving member 20 Proximal end 21 Exterior 22 Nozzle 23 Inside 24 Distal end 25 Internal volume 30 Insertion section 31 Motor 32 Pressure Jacket 34 Rolling diaphragm syringe 36 Hollow body 38 Internal volume 40 Distal end 42 Proximal end 44 Flexible sidewall 46 Closed end wall 48 Emission neck 50 central part 52 Drive member engagement portion 54 Housing 56 MUDS 58 Syringe 58a Syringe 58b Syringe 58c Syringe 60 Bulk Fluid Connector 62 MUDS Liquid Path 64 frames 66 Filling port 68 Discharge outlet, discharge pipe 70 Manifold 72 Valve 74 Liquid outlet line 76 Ports 119 Side wall 1310 Enter the desired flow profile for the injection. 1320 Injection phase begins 1330 Is the injection phase followed by a subsequent phase? 1340 steps completed 1350 Injection complete 1360 Evaluate current compliance status 1370 Predicting Subsequent Phase Compliance 1380 Calculate adjustments to the second stage flow profile 1390 Adjust the flow profile of subsequent stages 1410 Start first injection phase 1415 Measure the pressure of the first stage 1420 Approximate pressure of the second stage 1425 Calculate second stage compliance 1430 Second stage compliance > First stage compliance? 1435 No second stage flow regulation 1440 Calculate first stage compliance 1445 First stage flow rate 1450 Second Level Compliance 1455 Calculate the compliance Δ between the first and second stages 1460 Determine the second stage transition flow rate (Eq. 1) 1465 Start second injection stage with corrected flow rate 1470 After transition, increase second stage flow rate to programmed value

Claims

1. A fluid injector system for providing a multi-stage fluid injection, comprising: a first fluid reservoir configured to contain a first fluid of the multi-stage fluid injection; a second fluid reservoir configured to contain a second fluid of the multi-stage fluid injection; a first drive member operatively connected to the first fluid reservoir, the first drive member operable to dispense the first fluid of the multi-stage fluid injection; and a second drive member operatively connected to the second fluid reservoir, the second drive member 1. A method of operating a liquid injector system comprising: a second drive member operable to dispense the second liquid of the multi-stage liquid injection; liquid lines connected to the first liquid reservoir and the second liquid reservoir and configured to infuse the first liquid of the multi-stage liquid injection from the first liquid reservoir and the second liquid of the multi-stage liquid injection from the second liquid reservoir; and a control device configured to control operation of the first drive member and the second drive member, the method comprising: the control device moving the first drive member a distance corresponding to a first predetermined flow rate, the first fluid having a first viscosity; the control device moving the second drive member based on a flow rate profile different from a second predefined flow rate for a specified intermediate time interval or intermediate liquid volume, the second liquid having a second viscosity different from the first viscosity; the control device moving the second drive member a distance at least corresponding to the second predetermined flow rate; Equipped with the specified intermediate time interval is selected to allow a remaining portion of the first liquid to pass through the liquid line before commencing the step of moving the second drive member a distance at least corresponding to the second predetermined flow rate; the specified intermediate time interval is based on a system configuration, i.e., a capacitance of at least one of the first and second fluid reservoirs, a length of the fluid line, a diameter of the fluid line, a volume of the fluid line, a length of a catheter, a diameter of the catheter, a volume of the catheter, and any combination thereof; method.

2. The method of claim 1 , wherein the first viscosity is greater than the second viscosity.

3. 3. The method of claim 1 or 2, wherein the first liquid is selected from the group consisting of a contrast agent and a mixture of the contrast agent and saline in a specific ratio, and the second liquid is selected from the group consisting of saline and a mixture of the contrast agent and saline in a second specific ratio.

4. The method of claim 1 , wherein the second predetermined flow rate is approximately the same as the first predetermined flow rate.

5. A method according to any one of claims 1 to 4, wherein the flow profile is a flow rate less than the first predetermined flow rate.

6. A method according to any one of claims 1 to 5, wherein the flow profile is a flow rate that varies between zero and the second default flow rate over the specified intermediate time interval.

7. A method according to any one of claims 1 to 6, wherein the amount of movement of the second drive member for the specified intermediate time interval or intermediate liquid volume is determined by one or more of the volumetric capacity of the liquid line between the second liquid reservoir and the end of the liquid line, the capacitance of at least one of the first liquid reservoir and the second liquid reservoir, and injection system compliance.

8. A method according to any one of claims 1 to 7, wherein the flow profile is selected to minimize flow deviation over the specified intermediate time interval.

9. The flow profile is represented by the formula Q(Transition) = Q(Program Setting) - Q(Adjusted) 9. The method of claim 1, wherein Q(Transition) is a desired flow profile at the transition between the first and at least the second fluid, Q(Programmed) is a desired flow profile of the first and at least the second fluid, and Q(Adjusted) is a required adjustment of the flow rate of the second fluid, such that Q(Transition) at the transition between the first and at least the second fluid, i.e., the flow rate at the catheter tip, is approximately similar to Q(Programmed).

10. The flow profile is represented by the formula Q(t)=Q(p)-(C(1)-C(2)) / t(t) where Q(t) is the flow rate profile, Q(p) is the second predetermined flow rate, C(1) is the steady state system compliance at the first fluid stage, C(2) is the system compliance during infusion of the second fluid, and t(t) is the derived time to infuse a volume associated with the system compliance (C(2)).

11. the system compliance during infusion of the first fluid comprises a first compliance coefficient associated with one or more of the first fluid reservoir, a first infusion mechanism, and a set of tubing in operative fluid communication with the first fluid reservoir; 11. The method of claim 10, wherein the system compliance during infusion of the second fluid comprises a second compliance coefficient associated with one or more of the second fluid reservoir, a second infusion mechanism, and a tubing set in operative communication with the second fluid reservoir.

12. 12. The method of claim 1, wherein the first fluid reservoir is a first syringe operably connected to the first drive member of the fluid injector system, and the at least second fluid reservoir is at least a second syringe, the second syringe operably connected to at least the second drive member of the fluid injector system.

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