Reconstitution and injection system for single-dose contrast media - Patent Application 20070122997

Abstract

A fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution includes a first syringe containing a diluent, a container containing a solute contrast agent, a first valve configured to provide selective fluid communication between the container and the first syringe, and a controller programmed or configured to deliver the diluent into the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution and deliver the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 433,741, filed December 19, 2022, the disclosure of which is incorporated by reference in its entirety.

[0002] The present disclosure relates to fluid injector systems, and more particularly to fluid injector systems, related components, devices and methods for reconstituting a solute contrast agent and delivering the resulting reconstituted contrast media solution to a patient, which reduces costs and environmental impact by reducing the weight, volume and waste of transported contrast media. [Background technology]

[0003] Contrast agents for computed tomography (CT) and other imaging procedures are a one-size-fits-all product for most imaging procedures. Traditionally, contrast agents are supplied to healthcare professionals in liquid form (sometimes greater than 50% water by weight) and stored as a liquid until needed for a procedure. Methods of contrast agent supply and delivery have evolved into two main camps. The first camp focuses on using a single sterile, disposable contrast agent (e.g., bottle, bag) for each patient and is currently preferred by many healthcare professionals. In this case, all unused contrast agent is discarded, and subsequent patients are given an entirely new, disposable contrast agent. The second camp focuses on using larger volumes of sterile, disposable contrast agent that can be administered to multiple patients.

[0004] Current contrast agents and injectors are inefficient, ultimately leading to increased waste and costs. The disposable, single-use approach currently preferred by most healthcare professionals results in significant waste. A significant amount of contrast agent is not used before its expiration date and must be discarded. Because contrast agents are relatively expensive, such waste represents a significant cost to healthcare professionals and ultimately to patients.

[0005] Furthermore, contrast agents are relatively heavy and, as a result, must be contained in relatively large storage tanks. This complicates storage of the contrast agent by customers and can require them to set aside a significant amount of space for storage. Transportation costs can also be significant due to the size and weight of the contrast agent being shipped to customers. As mentioned above, manufactured contrast agents can be over 50% water by weight, so much of this cost is attributable to the presence of water, which is not an active ingredient. Due to their nature, conventional liquid contrast agents are most commonly shipped in glass bottles, which are fragile and require protective packaging. The volume and mass of the water and glass significantly affect the costs associated with manufacturing, dispensing, and using the contrast agent.

[0006] Furthermore, current methods of delivering contrast media have significant disposal issues. Glass bottles containing unused contrast media can be a significant source of waste and pose environmental concerns due to the iodine contained in the contrast media. Contrast media also have shelf-life and stability issues, often leading to the use of bulky glass containers as described above. Plastic containers generally cannot be used in place of glass because polymeric materials (e.g., plastic) can adversely affect the contrast media, rendering them unsuitable for patient use. Furthermore, liquid contrast media can crystallize regardless of the type of container in which it is stored (although suboptimal containers can also promote crystallization), which places an upper limit on the shelf life of the contrast media.

[0007] In view of the above, there is a need for fluid injector systems, related components, devices and methods for reconstituting a solute contrast agent and delivering the resulting reconstituted contrast agent to a patient, which reduce costs and environmental impact by reducing the weight, volume and waste of transported contrast agent. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] U.S. Patent No. 10,507,319 Summary of the Invention [Problem to be solved by the invention]

[0009] Accordingly, aspects of the present disclosure relate to non-limiting embodiments of a fluid injector system and associated components for reconstituting solute contrast agents prior to injection, which reduces costs and environmental impact by reducing the weight, volume, and waste of transported contrast agents. [Means for solving the problem]

[0010] According to one aspect of the present disclosure, a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution includes a first syringe containing a diluent, a container containing a solute contrast agent, a first valve configured to provide selective fluid communication between the container and the first syringe, and a controller programmed or configured to deliver the diluent to the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution and deliver the reconstituted contrast agent solution to an administration line configured to be fluidly connectable to a patient.

[0011] According to another aspect of the present disclosure, a flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution includes a first syringe, a second syringe, an administration line, and a container containing the solute contrast agent. The container is composed of a flexible membrane, a polymeric material capable of withstanding temperatures of at least 150°C, and an internal valve configured to receive a spike in the contrast agent line and passively seal the container when the spike is removed. The assembly further includes a diluent vessel containing a diluent, a first valve configured to provide selective fluid communication between one or more of the container, the first syringe, and the administration line, and a flushing agent vessel containing a flushing agent, a second syringe, and the administration line. The assembly further includes an agitator configured to receive the container, the agitator including a drive mechanism configured to shake the container during reconstitution, at least one heating element configured to apply heat to the container, and a controller. The controller is programmed or configured to control a first valve to deliver a diluent from a diluent reservoir into the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution, deliver the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient, and deliver the reconstituted contrast agent solution to the patient. The controller is further programmed or configured to control a second valve to deliver a cleaning agent from the cleaning agent reservoir into the administration line, and control the second valve to deliver the cleaning agent to the patient. Before the agitator receives the container, the container is further heat-treated so that the solute contrast agent reaches a temperature of at least 150°C.

[0012] According to another aspect of the present disclosure, a flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution includes a first syringe, a second syringe, a third syringe, a filter including at least one filter medium, an administration line, and a container containing the solute contrast agent. The assembly includes a first valve configured to provide selective fluid communication between one or more of the container, a diluent reservoir containing a diluent, the first syringe, and the filter, a second valve configured to provide selective fluid communication between one or more of the filter, the second syringe, and the administration line, and a third valve configured to provide selective fluid communication between one or more of the cleaning agent reservoir containing a cleaning agent, the third syringe, and the administration line. The assembly further includes a drive mechanism configured to receive the container and to shake the container during reconstitution, and a controller. The controller is programmed or configured to control a first valve to deliver a diluent from a diluent reservoir into the container, control an agitator to shake the container to reconstitute the solute contrast agent with the diluent into a reconstituted contrast agent solution, and control the first valve to deliver the reconstituted contrast agent solution into the filter. The controller is further programmed or configured to control a second valve to deliver the filtered reconstituted contrast agent solution into a second syringe and to deliver the filtered reconstituted contrast agent solution from the second syringe into the administration line. The controller is further programmed or configured to control a third valve to deliver a cleaning agent from the cleaning agent reservoir into a third syringe and to deliver the cleaning agent from the third syringe into the administration line. The administration line is configured to be fluidly connectable to a patient, and the controller is further programmed or configured to deliver the filtered reconstituted contrast agent solution and the cleaning agent through the administration line to the patient.

[0013] According to another aspect of the present disclosure, a method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system includes fluidly connecting a diluent reservoir containing a diluent to a first syringe of the fluid injector system; fluidly connecting a container containing a solute contrast agent to the first syringe of the fluid injector system; delivering the diluent into the container through the first syringe to reconstitute the solute contrast agent; shaking the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution; delivering the reconstituted contrast agent solution into the first syringe; and delivering the reconstituted contrast agent solution from the first syringe into an administration line of the fluid injector system.

[0014] According to another aspect of the present disclosure, a method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system includes fluidly connecting a diluent reservoir containing a diluent to a first syringe of the fluid injector system, fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system, fluidly connecting a container containing a solute contrast agent to the first syringe of the fluid injector system, and fluidly connecting a liquid contrast agent reservoir containing a liquid contrast agent to a third syringe of the fluid injector system. The method further includes delivering a cleaning agent from one or more cleaning agent reservoirs into a second syringe, delivering the cleaning agent from the second syringe into an administration line of the fluid injector system, delivering a liquid contrast agent from the liquid contrast agent reservoir into a third syringe, and delivering the liquid contrast agent from the third syringe into an administration line of the fluid injector system.

[0015] According to another aspect of the present disclosure, a container for containing a solute contrast agent for reconstitution in a fluid injector system, wherein the fluid injector system controls the operation of a first syringe and a second syringe in a manifold for the container and corresponding first and second valves, includes a flexible membrane defining a cavity therein for containing the solute contrast agent, the flexible membrane including a polymer material capable of withstanding temperatures of at least 150°C and allowing the cavity to be enlarged in size, and an internal valve in communication with the cavity. The internal valve is further configured to receive a spike associated with the fluid injector system such that (I) when the spike is inserted into the internal valve, the internal valve opens, thereby, under control of the first valve, alternately: (a) allowing diluent to flow from the first syringe through the first valve and the internal valve into the cavity and mix with the solute contrast agent to form a reconstituted contrast agent solution in the container; and (b) allowing the reconstituted contrast agent solution to flow from the cavity through the internal valve and the first valve to the first syringe, from which the fluid injector system injects the reconstituted contrast agent solution through the first valve and through the administration line to the patient; and (II) when the spike is removed from the internal valve, the internal valve closes.

[0016] Non-limiting illustrative examples of embodiments of the present disclosure are now described in the following numbered clauses:

[0017] Clause 1: A fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, comprising: a first syringe containing a diluent; a container containing the solute contrast agent; a first valve configured to provide selective fluid communication between the container and the first syringe; and a controller programmed or configured to deliver the diluent into the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution, and to deliver the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient.

[0018] Clause 2: The fluid injector system of clause 1, further comprising a second syringe and a second valve configured to provide selective fluid communication between one or more of a cleaning agent reservoir containing a cleaning agent, the second syringe, and the administration line.

[0019] Clause 3: The fluid injector system of clause 1 or 2, wherein the controller is further configured to deliver a cleaning agent into the administration line.

[0020] Clause 4: A fluid injector system described in any one of clauses 1 to 3, wherein the first valve is further configured to provide selective fluid communication between one or more of a diluent tank containing a diluent, a container, a first syringe, and an administration line.

[0021] Clause 5: A fluid injector system described in any one of clauses 1 to 4, wherein the fluid injector system further comprises an agitator configured to receive the container, the agitator comprising a drive mechanism configured to shake the container during reconstitution.

[0022] Clause 6: A fluid injector system described in any one of clauses 1 to 5, wherein the agitator further comprises at least one heating element configured to apply heat to the diluent contained in the container, the solute contrast agent, and the container during reconstitution.

[0023] Clause 7: A fluid injector system as described in any one of clauses 1 to 6, wherein the container is heat treated so that the solute contrast agent reaches a temperature of at least 150°C and so that the solute contrast agent is sterilized before the agitator receives the container.

[0024] Clause 8: A fluid injector system described in any one of clauses 1 to 7, wherein the container is heat-treated so that the solute contrast agent reaches a temperature of 200°C and so that the solute contrast agent is sterilized and purified by depyrogenation before the agitator receives the container.

[0025] Clause 9: A fluid injector system described in any one of clauses 1 to 8, further comprising a filter between the container and the first valve, the filter comprising at least one filter material configured to filter the reconstituted contrast agent solution.

[0026] Clause 10: A fluid injector system according to any one of clauses 1 to 9, wherein the filter is positively charged to remove endotoxins from the reconstituted contrast agent solution.

[0027] Clause 11: A fluid injector system described in any one of clauses 1 to 10, further comprising a pump configured to be fluidly connected to the container, the filter and the first syringe, the pump and filter being positioned between the spike of the contrast agent line and the first valve.

[0028] Clause 12: A second syringe, a third syringe, and a filter comprising at least one filter medium configured to filter the reconstituted contrast agent solution, wherein the first valve is further configured to provide selective fluid communication between one or more of the container, the first syringe, a diluent reservoir containing a diluent, and the filter, a second valve configured to provide selective fluid communication between one or more of the filter, the second syringe, and an administration line, a cleaning agent reservoir containing a cleaning agent, the third syringe, and an administration line. and a third valve configured to provide selective fluid communication between the first syringe and the second syringe; and wherein the controller is further programmed or configured to: deliver reconstituted contrast agent solution from the container to the first syringe, from the first syringe to the filter, and from the filter to the second syringe; deliver filtered reconstituted contrast agent solution from the second syringe to the administration line; deliver cleaning agent from the cleaning agent reservoir into the third syringe, and deliver cleaning agent from the third syringe to the administration line.

[0029] Clause 13: A fluid injector system described in any one of clauses 1 to 12, wherein the container comprises a flexible membrane comprising a polymer material capable of withstanding a temperature of at least 150°C and configured to expand, and an internal valve configured to receive a spike in the contrast agent line and configured to be in fluid communication with the first valve.

[0030] Clause 14: A fluid injector system as described in any one of clauses 1 to 13, wherein the internal valve is configured to passively seal the container when the spike is removed from the internal valve.

[0031] Clause 15: A fluid injector system described in any one of clauses 1 to 14, wherein the controller is further programmed or configured to deliver an unused portion of the reconstituted contrast agent solution from the first syringe into the container.

[0032] Clause 16: A fluid injector system described in any one of clauses 1 to 15, further comprising a third syringe and a third valve configured to provide fluid communication between one or more of the third syringe, the liquid contrast agent reservoir, and the administration line.

[0033] Clause 17: A fluid injector system described in any one of clauses 1 to 16, wherein the controller is further programmed or configured to deliver liquid contrast agent contained in the liquid contrast agent reservoir into the administration line.

[0034] Clause 18: A fluid injector system described in any one of clauses 1 to 17, wherein the controller is further programmed or configured to deliver an unused portion of the reconstituted contrast agent solution from the first syringe into the third syringe, and to deliver an unused portion of the reconstituted contrast agent solution from the third syringe into the liquid contrast agent reservoir.

[0035] Clause 19: A fluid injector system as described in any one of clauses 1 to 18, further comprising at least one reading device, wherein the container comprises at least one readable solute contrast agent identifier, the detergent tank comprises at least one readable detergent identifier, and the diluent tank comprises at least one readable diluent identifier, the at least one reading device is configured to scan and read the at least one readable solute contrast agent identifier, the at least one readable detergent identifier, and the at least one readable diluent identifier and communicate the identifier information to a controller, and the controller is further programmed or configured to process the identifier information and, based on the identifier information, start and stop fluid communication between one or more of the diluent tank, the container, the first syringe, and the administration line, and between one or more of the detergent tank, the second syringe, and the administration line.

[0036] Clause 20: A flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, the assembly comprising: a first syringe; a second syringe; an administration line; a container for containing the solute contrast agent, the container comprising: a flexible membrane; a polymeric material capable of withstanding a temperature of at least 150°C; and an internal valve configured to receive a spike on the contrast agent line and to passively seal the container when the spike is removed; a first valve configured to provide selective fluid communication between one or more of a diluent reservoir containing a diluent, the container, the first syringe, and the administration line; and a cleaning agent reservoir containing a cleaning agent, the second syringe, and the administration line. a second valve connected to the diluent reservoir; an agitator configured to receive the container, the agitator comprising: a drive mechanism configured to shake the container during reconstitution; and at least one heating element configured to apply heat to the container; and a controller programmed or configured to control the first valve to deliver a diluent from the diluent reservoir into the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution, deliver the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient, and deliver the reconstituted contrast agent solution to the patient, and to control the second valve to deliver a cleaning agent from the cleaning agent reservoir into the administration line and deliver the cleaning agent to the patient, wherein the container is heat-treated such that the solute contrast agent reaches a temperature of at least 150°C before the agitator receives the container.

[0037] Clause 21: A flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, the flow control assembly comprising: a first syringe; a second syringe; a third syringe; a filter comprising at least one filter medium; an administration line; a container for containing the solute contrast agent; a first valve configured to provide selective fluid communication between one or more of the container, a diluent reservoir for containing a diluent, the first syringe, and the filter; a second valve configured to provide selective fluid communication between one or more of the filter, the second syringe, and the administration line; a third valve configured to provide selective fluid communication between one or more of the cleaning agent reservoir for containing a cleaning agent, the third syringe, and the administration line; and an agitator configured to receive the container, the agitator comprising a drive mechanism configured to shake the container during reconstitution. and a controller programmed or configured to control a first valve to deliver a diluent from a diluent reservoir into the container, to control an agitator to shake the container to reconstitute a solute contrast agent with the diluent into a reconstituted contrast agent solution, to control the first valve to deliver the reconstituted contrast agent solution into a filter, to control a second valve to deliver the filtered reconstituted contrast agent solution into the second syringe and to deliver the filtered reconstituted contrast agent solution from the second syringe into an administration line, and to control a third valve to deliver a cleaning agent from the cleaning agent reservoir into the third syringe and to deliver the cleaning agent from the third syringe into the administration line, wherein the administration line is configured to be fluidly connectable to a patient, and the controller is further programmed or configured to deliver the filtered reconstituted contrast agent solution and the cleaning agent through the administration line to the patient.

[0038] Clause 22: A method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system, the method comprising the steps of: fluidly connecting a diluent tank containing a diluent to a first syringe of the fluid injector system; fluidly connecting a container containing a solute contrast agent to the first syringe of the fluid injector system; delivering the diluent into the container through the first syringe to reconstitute the solute contrast agent; shaking the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution; delivering the reconstituted contrast agent solution into the first syringe; and delivering the reconstituted contrast agent solution from the first syringe into an administration line of the fluid injector system.

[0039] Clause 23: The method of clause 22, further comprising the step of sterilizing the solute contrast agent in the container by heating the solute contrast agent in the container to a temperature of at least 150°C before fluidly connecting the container to the first syringe.

[0040] Clause 24: The method of clause 22 or 23, further comprising the step of purifying the reconstituted contrast agent solution by passing the reconstituted contrast agent solution through a filter comprising at least one filter medium before delivering the reconstituted contrast agent solution into the administration line of the fluid injector system.

[0041] Clause 25: A method according to any one of clauses 22 to 24, further comprising the steps of fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system, delivering the cleaning agent from the cleaning agent reservoir into the second syringe, and delivering the cleaning agent from the second syringe into an administration line of the fluid injector system.

[0042] Clause 26: The method of any one of clauses 22 to 25, further comprising purging air from the fluid injector system before fluidly connecting the container containing the solute contrast agent to the first syringe of the fluid injector system.

[0043] Clause 27: A method according to any one of clauses 22 to 26, further comprising the steps of fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system, and priming the administration line with at least one of a diluent from the diluent reservoir and a cleaning agent from the cleaning agent reservoir before connecting a container containing a solute contrast agent to the first syringe of the fluid injector system.

[0044] Clause 28: The method of any one of clauses 22 to 27, further comprising delivering an unused portion of the reconstituted contrast agent solution from the first syringe into the container.

[0045] Clause 29: The method of clauses 22 to 28, further comprising the steps of removing a container containing an unused portion of the reconstituted contrast agent solution from the fluid injector system and sending the container to a recycling facility to recover the active component of the reconstituted contrast agent solution.

[0046] Clause 30: The method of any one of clauses 22 to 29, further comprising the step of delivering an unused portion of the reconstituted contrast agent solution from the first syringe into the liquid contrast agent reservoir.

[0047] Clause 31: The method of any one of clauses 22 to 30, further comprising the step of using a controller of the fluid injector system to determine whether the container is approved for use in an injection procedure based on at least one factor.

[0048] Clause 32: The method of any one of clauses 22 to 31, wherein the at least one factor includes at least one of the following: the expiration date of the container; the solute contrast agent being unsuitable for the injection procedure; the container containing an unauthorized substance; the container not containing a sufficient amount of solute contrast agent required for the injection procedure; and the container having been used previously.

[0049] Clause 33: The method of any one of clauses 22 to 32, further comprising the step of aborting the injection procedure in response to the controller determining that the container is not approved for use in the injection procedure.

[0050] Clause 34: A method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system, the method comprising the steps of: fluidly connecting a diluent reservoir containing a diluent to a first syringe of the fluid injector system; fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system; fluidly connecting a container containing a solute contrast agent to the first syringe of the fluid injector system; fluidly connecting a liquid contrast agent reservoir containing a liquid contrast agent to a third syringe of the fluid injector system; delivering the cleaning agent from one or more cleaning agent reservoirs into the second syringe; delivering the cleaning agent from the second syringe into an administration line of the fluid injector system; delivering the liquid contrast agent from the liquid contrast agent reservoir into the third syringe; and delivering the liquid contrast agent from the third syringe into an administration line of the fluid injector system.

[0051] Clause 35: A container for containing a solute contrast agent for reconstitution in a fluid injector system, wherein the fluid injector system is used to control the operation of a first syringe and a second syringe in a manifold for the container, and corresponding first and second valves, the container comprising: a flexible membrane defining a cavity therein for containing the solute contrast agent, the flexible membrane including a polymer material capable of withstanding a temperature of at least 150°C and allowing the cavity to be enlarged in size; and an internal valve communicating with the cavity, wherein: (I) when a spike associated with the fluid injector system is inserted into the internal valve, the internal valve opens and and (ii) an internal valve configured to receive a spike such that, when the spike is removed from the internal valve, the internal valve closes.

[0014] Further details and advantages of the various examples described herein will become apparent from a review of the following detailed description of the various examples in conjunction with the accompanying drawings.

[0052] Further advantages and details are explained in more detail below with reference to exemplary embodiments shown in the accompanying schematic drawings. [Brief explanation of the drawings]

[0053] [Figure 1] 1 is a schematic diagram of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 2] 2 is a schematic diagram of the fluid injector system of FIG. 1 in a first position. [Figure 3]2 is a schematic diagram of the fluid injector system of FIG. 1 in a second position. [Figure 4] 2 is a schematic diagram of the fluid injector system of FIG. 1 in a third position. [Figure 5] 2 is a schematic diagram of the fluid injector system of FIG. 1 in a fourth position. [Figure 6] FIG. 2 is a schematic diagram of the fluid injector system of FIG. 1 in a fifth position. [Figure 7] FIG. 2 is a schematic diagram of the fluid injector system of FIG. 1 in a sixth position. [Figure 8] FIG. 2 is a schematic diagram of the fluid injector system of FIG. 1 in a seventh position. [Figure 9] FIG. 2 is a schematic diagram of the fluid injector system of FIG. 1 in an eighth position. [Figure 10A] 1 is a side perspective view of a non-limiting embodiment of a syringe, valve, and distribution manifold of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 10B] 1 is a side view of a non-limiting embodiment of a syringe, valves, distribution manifold, tubing, filters, and spikes of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 11] 1 is a cross-sectional front view of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 12] 1 is a side perspective view of a non-limiting embodiment of a flow control assembly of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 13A] 1 is a front perspective view of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 13B] 1 is a cross-sectional side view of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 14] 1 is a cross-sectional top view of a non-limiting embodiment of an agitator of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 15]1 is a schematic diagram of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 16A] 1 is a perspective view of a non-limiting embodiment of a filter of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 16B] 1 is a perspective view of a non-limiting embodiment of a filter of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 17] 1 is a schematic diagram of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 18] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a first position. [Figure 19] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a second position. [Figure 20] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a third position. [Figure 21] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a fourth position. [Figure 22] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a fifth position. [Figure 23] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a sixth position. [Figure 24] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in a seventh position. [Figure 25] FIG. 18 is a schematic diagram of the fluid injector system of FIG. 17 in an eighth position. [Figure 26A] 1 is a perspective view of a non-limiting embodiment of a container containing a solute contrast agent of a fluid injector system according to one aspect or example of the present disclosure; FIG. [Figure 26B] FIG. 26B is an exploded perspective view of the container of FIG. 26A. [Figure 27A] 1 is a perspective view of a non-limiting embodiment of a container containing a solute contrast agent of a fluid injector system according to one aspect or example of the present disclosure; FIG. [Figure 27B] FIG. 27B is a side view of the container of FIG. 27A. [Figure 27C] FIG. 27B is a perspective view of Detail A of the container of FIG. 27A. [Figure 28] 27A and 27B connected to a contrast tube of a fluid injector system, according to one embodiment or example of the present disclosure. FIG. [Figure 29A] FIG. 27D is a top view of the container of FIGS. 27A to 27C in a state where fluid is being dispensed. [Figure 29B] FIG. 27D is a top view of the container of FIGS. 27A to 27C with fluid being withdrawn. [Figure 29C] FIG. 27D is a top view of the container of FIGS. 27A to 27C separated from the contrast agent tube. [Figure 30A] FIG. 27D is a side view of a spike fully inserted into the container of FIGS. 27A-27C, according to one embodiment or example of the present disclosure. [Figure 30B] FIG. 27D is a side view of a spike partially inserted into the container of FIGS. 27A to 27C. [Figure 30C] FIG. 27D is a side view of the spike being removed from the container of FIGS. 27A to 27C. [Figure 31A] FIG. 2 is a top view of a non-limiting embodiment of a distribution manifold of a fluid injector system according to one aspect or example of the present disclosure. [Figure 31B] 1 is a perspective view of a non-limiting embodiment of a distribution manifold of a fluid injector system according to one aspect or example of the present disclosure. FIG. [Figure 32A] 1 is a side cross-sectional view of a non-limiting embodiment of a valve of a fluid injector system according to one aspect or example of the present disclosure. [Figure 32B] 1 is a perspective view of a non-limiting embodiment of a valve of a fluid injector system according to one aspect or example of the present disclosure; FIG. [Figure 33A] FIG. 1 is a perspective view of a non-limiting embodiment of an agitator for a fluid injector system according to one aspect or example of the present disclosure. [Figure 33B] FIG. 33B is a side view of the agitator of FIG. 33A. [Figure 33C]FIG. 33B is a perspective view of the agitator of FIG. 33A in a retracted position according to one embodiment or example of the present disclosure. [Figure 33D] FIG. 33B is a perspective view of the agitator of FIG. 33A in an extended position according to one embodiment or example of the present disclosure. [Figure 34] FIG. 1 is a side view of a non-limiting embodiment of a housing, stand, and agitator of a fluid injector system according to one aspect or example of the present disclosure. [Figure 35A] FIG. 35 is a side perspective view of the agitator of FIG. 34. [Figure 35B] FIG. 35 is a perspective view from above of the stirrer of FIG. 34. [Figure 36] FIG. 35 is a schematic diagram of the agitator of FIG. 34. [Figure 37A] FIG. 35 is a side view of the agitator of FIG. 34. [Figure 37B] FIG. 35 is a perspective view of the counterweight of the agitator of FIG. 34. [Figure 38] 1 is a schematic diagram of a non-limiting embodiment of a fluid injector system according to one aspect or example of the present disclosure. [Figure 39] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a first position. [Figure 40] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a second position. [Figure 41] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a third position. [Figure 42] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a fourth position. [Figure 43] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a fifth position. [Figure 44] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a sixth position. [Figure 45] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in a seventh position. [Figure 46] FIG. 39 is a schematic diagram of the fluid injector system of FIG. 38 in an eighth position. [Figure 47]FIG. 2 is a schematic diagram of the fluid injector system of FIG. 1 in a ninth position. [Figure 48] FIG. 10 is a schematic diagram of the fluid injector system of FIG. 1 in a tenth position. [Figure 49] FIG. 1 is a sequence diagram of a non-limiting embodiment of a method for reconstituting a solute contrast agent using a fluid injector system and injecting the resulting reconstituted contrast agent solution, according to one aspect or example of the present disclosure. [Figure 50] 1 is a sequence diagram of a non-limiting embodiment of a method for verifying components of a fluid injector system according to one aspect or example of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0054] Corresponding reference characters indicate corresponding parts throughout the several views. The examples set forth herein illustrate exemplary embodiments of the present disclosure, and such embodiments should not be construed as limiting the scope of the present disclosure in any way.

[0055] It is to be understood that the present disclosure may contemplate various alternative modifications and step sequences unless expressly specified 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 and non-limiting embodiments or aspects of the present disclosure. Hence, specific dimensions and other physical characteristics related to the embodiments or aspects disclosed herein are not to be considered limiting, unless otherwise indicated.

[0056] For purposes of the following description, when oriented in the drawings, the terms "end," "upper," "lower," "right," "left," "vertical," "horizontal," "top," "bottom," "lateral," "longitudinal," and derivatives thereof, shall refer to an embodiment or aspect of the present disclosure. However, it should be understood that an embodiment or aspect may assume various alternative variations and step sequences unless expressly specified to the contrary. Spatial or directional terms such as "left," "right," "inner," "outer," "upper," "lower," etc., should not be considered limiting as the present disclosure may assume various alternative orientations.

[0057] All numbers used in this specification and claims should be understood to be modified in all instances by the term "about." The terms "approximately," "about," and "substantially" refer to a range of plus or minus 10% of the stated value.

[0058] As used herein, "at least one of" is synonymous with "one or more of." For example, the phrase "at least one of A, B, and C" means any one of A, B, and C, or any combination of any two or more of A, B, and C. For example, "at least one of A, B, and C" includes one or more of A alone, or one or more of B alone, or one or more of C alone, or one or more of A and one or more of B, or one or more of A and one or more of C, or one or more of B and one or more of C, or one or more of all of A, B, and C. Similarly, as used herein, the term "at least two of" is synonymous with "two or more of." For example, the phrase "at least two of D, E, and F" means any combination of any two or more of D, E, and F. For example, "at least two of D, E, and F" includes one or more of D and one or more of E, or one or more of D and one or more of F, or one or more of E and one or more of F, or one or more of all of D, E, and F.

[0059] As used herein, aspects, components, elements, structures, operations, steps, functions, instructions, and the like should not be construed as critical or essential unless expressly stated as such. Also, as used herein, the articles "a" and "an" are intended to include one or more items and may be used interchangeably with "one or more" and "at least one." As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. When only one item is intended, the term "one" or similar terminology is used. Also, as used herein, terms such as "has," "have," and "having" are intended to be open-ended terms. Furthermore, the phrase "based on" is intended to mean "based at least partially on," unless otherwise specified. Additionally, the phrase "based on" is intended to mean "based at least partially on," unless otherwise specified.

[0060] The term "distal," when used with respect to a component of a fluid injector system, such as a fluid reservoir, syringe, or fluid line, refers to the portion of the component closest to the patient. The term "proximal," when used with respect to a component of a fluid injector system, such as a fluid reservoir, syringe, or fluid line, refers to the portion of the component closest to the injector of the fluid injector system (i.e., the portion of the component farthest from the patient). The term "proximal," when used with respect to a syringe of a multi-patient disposable set, refers to the portion of the syringe closest to the piston for delivering fluid from the syringe. The term "upstream," when used with respect to a component of a fluid injector system, such as a fluid reservoir, syringe, or fluid line, refers to the direction away from the patient and toward the injector of the fluid injector system. For example, when a first component is referred to as being "upstream" of a second component, the first component is located closer to the injector than the second component. The term "downstream," when used with reference to a component of a fluid injector system, such as a fluid reservoir, syringe, or fluid line, refers to a direction away from the injector of the fluid injector system toward the patient. For example, when a first component is referred to as being "downstream" of a second component, the first component is located closer to the patient than the second component.

[0061] Embodiments of the present disclosure generally relate to a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, which may include a first syringe containing a diluent, a container containing a solute contrast agent, a first valve configured to provide selective fluid communication between the container and the first syringe, and a controller. The controller may be programmed or configured to deliver the diluent into the container to reconstitute the solute contrast agent into a reconstituted contrast agent solution and deliver the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient.

[0062] In this manner, embodiments of the present disclosure enable fluid injector systems, associated components, devices and methods for reconstituting solute contrast agents and delivering the resulting reconstituted contrast agent solution to a patient, which reduce costs and environmental impact by reducing the weight, volume and waste of transported contrast agents.

[0063] With reference to the drawings, in which like reference numerals refer to like parts throughout the several views, the present disclosure generally relates to systems, related components, devices, and methods for reconstituting a solute contrast agent and delivering the resulting reconstituted contrast agent solution. While the present disclosure is generally described in the context of computed tomography (CT) imaging procedures, the systems, devices, and methods described herein may be used for applications other than CT, where reconstitution and intravenous injection of a contrast agent is indicated. Such procedures include, but are not limited to, X-ray, magnetic resonance imaging (MRI), and ultrasound procedures. It should also be understood that the systems, devices, and methods disclosed herein are applicable to the reconstitution and injection of other solutes, such as therapeutic agents, pharmaceuticals, and drugs. It should further be understood that the solute may be in various physical states or forms. For example, the solute may be a solid, such as a dry powder, or a concentrated liquid.

[0064] Referring first to FIG. 1 , FIG. 1 is a schematic diagram illustrating a non-limiting embodiment of a fluid injector system 1000 for reconstituting and injecting a solute contrast agent according to the present disclosure. The fluid injector system 1000 may include a flow control assembly having one or more syringes 120 a, 120 b fluidly connected to a distribution manifold 140. The distribution manifold 140 may include multiple input / output ports that can be opened or closed by corresponding valves 142 a, 142 b, thereby providing selective fluid communication between the various components of the system 1000 described herein. While the exemplary fluid injector system 1000 shown in FIG. 1 includes two syringes 120 a, 120 b and two valves 142 a, 142 b, the system 1000 may include more or fewer of these components as needed to perform the desired injection procedure. For example, in addition to the two-barrel configuration shown in FIG. 1, the present disclosure also contemplates a three-barrel configuration, and associated valve manifold structures and components, as shown and described with reference to FIGS. 17-25 and 38-46.

[0065] Thus, fluid injector system 1000 may include a first syringe 120a containing a diluent (e.g., water for injection), a container 300 containing a solute contrast agent, and a first valve 142a configured to provide selective fluid communication between container 300 and first syringe 120a. System 1000 may further include a controller 900 programmed or configured to deliver the diluent into container 300 to reconstitute the solute contrast agent into a reconstituted contrast agent solution, and deliver the reconstituted contrast agent solution into an administration line 510 configured to be fluidly connectable to a patient.

[0066] In the exemplary fluid injection system shown in FIG. 1 , syringes 120a, 120b, distribution manifold 140, and valves 142a, 142b may be configured as a “day set” or “multiuse disposable set” (MUDS), i.e., an assembly that can be replaced once a day and used to perform multiple injection procedures on multiple patients. Examples of syringes 120a, 120b and associated housings, as well as electromechanical components for operating syringes 120a, 120b, are described in U.S. Patent No. 6,223,999, the disclosure of which is incorporated herein by reference in its entirety. However, it should be noted that the features of distribution manifold 140 of the present disclosure described in connection with FIGS. 1-9, 15, 17-25, 31-32, and 30-48 herein are not disclosed in U.S. Patent No. 6,223,999.

[0067] System 1000 may further include a diluent reservoir, such as water for injection (WFI) reservoir 200 shown in Figure 1. Distribution manifold 140 may be fluidly connected to one or more water for injection (WFI) reservoirs 200 containing a diluent, such as water or another fluid suitable for reconstituting a dry (e.g., powdered) solute contrast agent. First valve 142a may be configured to provide selective fluid communication between one or more WFI reservoirs 200, container 300, first syringe 120a, and administration line 510.

[0068] Ideally, water for use in the WFI tank 200 should be sterile, non-pyrogenic, distilled water in a single-dose container for intravenous administration after the addition of appropriate solutes. The WFI tank 200 may also be used as a dispensing container for use with diluents. Preferably, no antimicrobial agents or other substances should be added to the WFI. Furthermore, the WFI should exhibit a pH range of 5.0 to 7.0, preferably 5.5, and an osmolarity of 0. WFI is generally available in bulk, i.e., 0.5 L or 1.0 L bags. Notably, one or more WFI tanks 200 are fluidly connected to the first valve 142a of the distribution manifold 140 via the main water tubing 202.

[0069] The container 300 containing the solute contrast agent may be a pouch 300, described below with reference to FIGS. 27A-28, or another suitable container. The pouch 300 may contain a therapeutic agent (e.g., contrast agent) in dry (e.g., powdered) form and may include a valve 310 fluidly connected to the first valve 142a of the distribution manifold 140 via the contrast agent tubing 206. The system 1000 may include an agitator 600 configured to receive the container 300. The agitator 600 may include a drive mechanism and / or other mechanical features for vibrating, shaking, rotating, translating, etc., the pouch 300 during reconstitution of the contrast agent therein. Non-mechanical means (e.g., heat) may be used to provide energy to the mixture of powder and WFI to ensure proper reconstitution of the contrast agent solution. In some non-limiting embodiments, the agitator 600 may include at least one heating element configured to apply heat to the container 300 and the solute contrast agent during reconstitution. In some non-limiting embodiments, agitator 600 may be configured to facilitate other non-mechanical means of energy transfer to container 300 for reconstitution, instead of or in addition to mechanical and / or thermal energy. For example, agitator 600 may be configured to deliver electrical, magnetic, electromagnetic, optical, sonic, radiative, or other energy to container 300 for reconstitution.

[0070] System 100 may also include a irrigant reservoir 500 containing a irrigant, a second syringe 120b, and a second valve 142b configured to provide selective fluid communication between one or more of second syringe 120b and administration line 510. Accordingly, controller 900 may be further programmed or configured to deliver the irrigant into administration line 510. The irrigant reservoir may contain a saline solution including sodium chloride (NaCl) for use in cleaning / priming system 1000. Administration line 510 may be an IV set for connection to a patient. Administration line / IV set 510 may include, for example, a needle for insertion into a patient's vein.

[0071] Each of valves 142a, 142b may be a multi-position stopcock, for example, as shown in Figures 32A and 32B, configured to facilitate selective control of fluid flow between various system components connected thereto. First valve 142a may facilitate selective fluid flow control between one or more of WFI reservoir 200, pouch 300, first syringe 120a, and dispensing line 510. Second valve 142b may facilitate selective fluid flow control between second syringe 120b, cleaning agent reservoir 500, and dispensing line 510.

[0072] The controller 900 may be configured to control the operation of the various components of the injector system 1000 described herein. The controller 900 includes at least one processor and is configured to perform one or more operations of the fluid injector system 1000 according to one or more injection protocols stored in a memory of or accessible by the controller 900.

[0073] To ultimately deliver a predetermined dose of contrast agent to a patient, the dry contrast agent contained in pouch 300 must first be reconstituted to obtain a liquid form of contrast agent as an injectable (i.e., safe for injection into a patient) contrast agent solution. Reconstitution and injection of the contrast agent is accomplished by operating syringes 120a, 120b and valves 142a, 142b in a predetermined sequence, as shown in FIGS. 2-9. The following description of FIGS. 2-9 omits the steps of purging / priming system 1000 because these operations are typically performed only once a day on the system, and therefore, purging and priming do not represent the majority of the system's use. Details of the purging and priming operations are described in detail herein with reference to FIGS. 45-48.

[0074] Referring now to FIG. 2 , water from the WFI bath 200 must first be injected into the pouch 300. To that end, the first valve 142a is positioned to establish fluid communication between the first syringe 120a and the main water tube 202. The piston 122a associated with the first syringe 120a is retracted proximally to draw a predetermined amount of fluid from the WFI bath 200 into the first syringe 120a. Next, as shown in FIG. 3 , the first valve 142a is positioned to establish fluid communication between the first syringe 120a and the contrast tube 206. The piston 122a associated with the first syringe 120a is advanced distally to inject the predetermined amount of fluid previously drawn from the WFI bath 200 into the first syringe 120a through the contrast tube 206 and into the pouch 300. When fluid is injected into pouch 300, the fluid mixes with and reconstitutes the dried contrast agent within pouch 300 to produce a reconstituted contrast agent solution. Agitator 600 may be activated during reconstitution of the contrast agent to vibrate and heat pouch 300 and increase the effectiveness (e.g., speed and uniformity) of the reconstituted contrast agent. When fluid is injected into pouch 300, the walls of pouch 300 may stretch to accommodate the increased volume, as described in detail herein with reference to FIGS. 26A-28 .

[0075] Once the contrast agent in pouch 300 is reconstituted, first valve 142a is maintained in the same position as in Figure 3 to maintain fluid communication between first syringe 120a and contrast agent tubing 206. Then, as shown in Figure 4, piston 122a associated with first syringe 120a may be retracted and reconstituted contrast agent may be drawn from pouch 300 into first syringe 120a.

[0076] At this stage, the reconstituted contrast agent may be suitable for injection, depending on the state of the contrast agent and whether it has been pre-processed to remove particulates and / or impurities (e.g., endotoxins, killed viruses / bacteria), or whether the solute contrast agent contains endotoxins or other impurities when container 300 is filled. In some non-limiting embodiments, container 300 may be heat-treated to cause the solute contrast agent to reach a temperature of at least 150°C and to sterilize the solute contrast agent before the agitator receives the container. In some non-limiting embodiments, container 300 may be heat-treated to cause the solute contrast agent to reach a temperature of 200°C and to sterilize and clean the solute contrast agent by depyrogenation before the agitator receives the container. In some non-limiting embodiments, container 300 may be aseptically filled using a non-pyrogenic (endotoxin-free) solute contrast agent.

[0077] If pouch 300 and solute contrast agent have been previously heat-treated to undergo depyrogenation (described in detail below with reference to FIGS. 26A-27C), the reconstituted contrast agent in first syringe 120a is ready for safe delivery to administration line 510 and injection into a patient. However, if the solute contrast agent has not been treated prior to reconstitution, or if further removal of particulates and / or impurities is indicated, then the particulates / impurities are removed from the reconstituted contrast agent by filtration prior to delivery to administration line 510 and injection into a patient. Filtration aspects of the present disclosure are described herein with reference to FIGS. 15-25.

[0078] Once the reconstituted contrast agent has been loaded into the first syringe 120a, the first valve 142a may be positioned to establish fluid communication between the first syringe 120a and the administration line 510, as shown in FIG. 5. The first piston 122a associated with the first syringe 120a may be advanced to inject the injectable reconstituted contrast agent solution toward the administration line 510. As shown in FIG. 6, while the reconstituted contrast agent is being drawn into the syringe 120a, the valve 142b may be positioned to establish fluid communication between the second syringe 120b and the wash agent tube 502. The second piston 122b associated with the second syringe 120b may be retracted to draw wash agent into the second syringe 120b. Once the injectable reconstitution contrast agent solution has been loaded into the first syringe 120a and the cleaning agent has been loaded into the second syringe 120b, the valves 142a, 142b may be positioned to establish fluid communication between the syringes 120a, 120b and the administration line 510. The first piston 122a and the second piston 122b may then be advanced to inject the injectable reconstitution contrast agent solution and the cleaning agent (e.g., saline) into the administration line 510 and the patient, as shown in FIG.

[0079] 5, 7, and 8 are used for illustrative purposes to show fluid communication between a syringe (e.g., first syringe 120a) and administration line 510 via manifold 140. However, it should be understood that fluid communication between syringe 120a and administration line 510 may be established via one or more other valves (e.g., second valve 142b), or alternatively, by directional communication through a conduit (e.g., conduit 170) of manifold 140, as described herein with reference to FIGS.

[0080] Some injection procedures may not require the entire amount of reconstituted contrast agent produced from pouch 300. In such procedures, after the injection procedure is completed, an excess of liquid contrast agent is present in first syringe 120a. This unused contrast agent can be returned in liquid form to pouch 300 and stored for recycling. With reference to FIGS. 8-9, controller 900 can be configured to deliver an unused portion of the injectable reconstituted contrast agent solution from first syringe 120a to container 300. The process of recovering the unused contrast agent is illustrated in FIGS. 8 and 9.

[0081] Referring to FIG. 8 , first syringe 120a is partially filled with unused contrast media after an injection procedure. In such a case, piston 122a is in an intermediate position within syringe 120a, and the volume between piston 122a and the distal end of syringe 120a is filled with unused contrast media. As shown in FIG. 9 , first valve 142a is positioned to establish fluid communication between first syringe 120a and pouch 300. Piston 122a is advanced to deliver unused contrast media from first syringe 120a into pouch 300. Pouch 300 may then be disconnected from agitator 600 and contrast line 206 and may undergo further recycling or regeneration processes.

[0082] Actuation of valves 142a, 142b to various positions as shown in Figures 2-9 may be performed automatically by controller 900 according to a pre-programmed injection procedure. Similarly, advancement / retraction of pistons 122a, 122b as shown in Figures 2-9 may be performed automatically by controller 900 according to a pre-programmed injection procedure.

[0083] Having outlined the process of reconstituting and injecting contrast media from pouch 300, further details of a non-limiting embodiment of fluid injector system 1000 having a dual-barrel fluid control configuration will now be described. Referring now to Figures 10A and 10B, Figure 10A illustrates a non-limiting embodiment of syringes 120a, 120b, valves 142a, 142b, and distribution manifold 140 of fluid injector system 1000. Valves 142a, 142b of system 1000 may be attached to the top of manifold 140, and syringes 120a, 120b may be connected to the bottom of manifold 140 such that valves 142a, 142b control flow to and from syringes 120a, 120b. The distribution manifold may further include ports 150, 152, 158, 160 for fluidly connecting to various other components of the system 1000. As shown in FIG. 10B, the ports 150, 152, 158 may facilitate fluid connections between the syringes 120a, 120b and the various lines 202, 206, 502. FIG. 10B also shows the connection of a spike 320 to the contrast agent tubing 206 for insertion into a container, such as a pouch 300. Additionally, FIG. 10B shows an optional filtration module 400 for removing particulates and / or impurities from the reconstituted contrast agent, as described below with reference to FIGS. 15-25.

[0084] 11-15, non-limiting embodiments of a fluid injector system 1000 and the illustrated flow control assembly may be the same as or similar to the system 1000 shown and described with reference to FIGS. 1-9. In these embodiments, the components of the flow control assembly are substantially similar to the embodiment of FIGS. 1-9, and like numbers are used to indicate like components. As shown, the system 1000 may include syringes 120a, 120b, an administration line 510, a container 300 containing a solute contrast agent, valves 142a, 142b, an agitator 600, and a controller 900. As shown in FIG. 11, the controller 900 may be a computer or tablet with at least one processor.

[0085] In an exemplary embodiment, system 1000 may include a filtration module 400 (described below with reference to FIGS. 16A and 16B) between container 300 and first valve 142a. In some non-limiting embodiments, system 1000 may further include a pump 450 configured in fluid communication with container 300, filtration module 400, and first syringe 120a. Filtration module 400 and pump 450 may be disposed between spike 320 of contrast line 206 and first valve 142a, as shown in FIG. 11 . Filtration module 400 may be provided, and in some non-limiting embodiments, the filtration module may be configured to remove only coarse particles (e.g., particles 10-20 microns or larger) or may be configured to remove small particles using only a small pore filter, which requires the use of an auxiliary pump, such as pump 450, to help push the fluid. Other embodiments may not use a filtration module at all, as dry heat sterilization may provide sufficient temperatures to eliminate the need for filtration to remove endotoxins.

[0086] 13A and 13B, the system 1000 may include a housing 110 for containing and protecting the flow control assembly and other components of the system 1000. The system 1000 may further include a stand 112 for mounting various components of the system 1000. As shown in FIG. 13A, the housing 110 may enclose the system such that only the controller 900 is exposed to allow a user to monitor and control the system 1000, and the administration line 510 is exposed for connection to a patient.

[0087] 13A and 13B, the housing 110 may have compartments, such as a lid 114, that open and close to expose components of the system 1000 for setup, maintenance, or other interaction with components of the flow control assembly of the system 1000. For example, as shown in FIG. 14, the lid 114 can be opened to provide access to the agitator 600 and plate 610 to introduce the vessel 300 into the system. Other openings may be provided to provide access to the syringes 120a, 120b, valves 142a, 142b, pistons 122a, 122b, diluent reservoir 200, detergent reservoir 500, water tubing 202, detergent tubing 502, etc., for setup or maintenance of the system 1000.

[0088] As shown in FIGS. 13B and 14 , the agitator 600 may be attached to the housing 110 or stand 112 of the fluid injector system 1000 via a bracket 604. The agitator 600 may be configured to receive the container 300 and may include a movable plate 610 to which the container 300 can be secured, thereby fluidly connecting the pouch 300 to the contrast line 206 through a spike 320 during reconstitution. The container 300 may be secured to the plate 610 so that a solute contrast agent identifier, such as an identification mark 312, is visible to a reader, as described below with reference to FIG. 50 . A motor (e.g., a servo motor 620) may also be attached to the agitator 600 to facilitate the shaking motion of the plate 610 during reconstitution. Further details of an exemplary embodiment of the agitator 600 are shown and described below with reference to FIGS. 33A-33D .

[0089] Referring now to FIG. 15, FIG. 15 is a schematic diagram of a non-limiting embodiment of the fluid injector system 1000 shown in FIGS. 11-14. In this exemplary embodiment, the fluid control assembly includes two barrels (syringes 120a, 120b), a filtration module 400, and a pump 450. The operation of the system shown in FIGS. 11-15 can be substantially the same as or similar to that described with reference to FIGS. 1-9, with the addition of the optional filtration module 400 and pump 450. Accordingly, the first valve 142a can be configured to provide selective fluid communication between one or more WFI reservoirs 200, the first syringe 120a, the filtration module 400, the pump 450, and the container 300. During reconstitution, after diluent is drawn from the WFI reservoir 200 into the first syringe 120a, the WFI passes through the filtration module 400 and the pump 450 as it is delivered to the container 300. Because the WFI is ideally already sterile, passing the WFI through filtration module 400 to reach the solute contrast agent contained in container 300 has little or no effect on the WFI or the filtration module. Similarly, because the WFI is ideally non-pyrogenic, there is little or no resistance as the WFI passes through filtration module 400, and pump 450 does not have to be operated to deliver the WFI into container 300.

[0090] Once diluent / WFI is delivered to container 300 and the solute contrast agent is reconstituted into a reconstituted contrast agent solution, the contrast agent is drawn through contrast agent tubing 206 and valve 142a into first syringe 120a and passes through pump 450 and filtration module 400. As described with reference to FIGS. 11 through 15 , filtration module 400 may remove only coarse particles or may use a small-pore filter to remove smaller particles. Removal of these particles can create resistance as the reconstituted contrast agent passes through filtration module 400 and may require the use of pump 450 to facilitate pushing the reconstituted contrast agent through the filter. After the reconstituted contrast agent passes through pump 450 and filtration module 400 and is drawn into first syringe 120a by retracting piston 122a (assisted by pump 450, which pushes the flow), the reconstituted contrast agent is contained in first syringe 120a in a state suitable for delivery to administration line 510 and ultimately to the patient.

[0091] 16A and 16B, a non-limiting embodiment of a filtration module 400 according to the present disclosure may include at least one filter medium and may be configured to filter the reconstituted contrast agent solution. Filtration module 400 may include one or more filter units configured to remove particulates, endotoxins, bacteria, viruses, etc. from the reconstituted contrast agent.

[0092] While the embodiment of the filtration module 400 shown in FIGS. 16A and 16B includes a single filter housing 410, in some embodiments, several filter housings 410 may be fluidly connected in series and / or parallel to improve filtration efficiency. In the embodiment shown in FIGS. 16A and 16B, the filter housing 410 includes an inlet port 412 configured to connect to a filtration inlet line 402 (as shown in FIG. 17) and an outlet port 414 configured to connect to a first filtration outlet line 404. The filter housing 410 houses a filter medium 416 selected to remove various contaminants from the reconstituted contrast agent. The filter medium 416 may be a porous structure, such as a polyethersulfone (PES) membrane, configured to capture specific impurities (including particulates and bacteria) larger than a predetermined size, such as 0.2 microns. The filter medium 416 may be further configured to bind specific impurities (such as endotoxins). The filtration module 400 may exhibit one or more modes of action, such as those targeting the size, charge, and / or affinity of various pathogens or molecules. The filter media 416 may be positively charged to remove negatively charged particles (eg, endotoxins).

[0093] Referring now to FIG. 17 , FIG. 17 is a schematic diagram illustrating a non-limiting embodiment of a fluid injector system 1000 according to the present disclosure configured in a three-barrel configuration. As shown in the illustrated embodiment, system 1000 may include a flow control assembly having a third syringe 120c and a corresponding third valve 142c, such that the system includes three syringes 120a, 120b, and 120c fluidly connected to a distribution manifold 140. In this exemplary three-barrel embodiment, a filtration module 400 is included in system 1000, and first syringe 120a, second syringe 120b, and their respective associated components may be configured to function in connection with reconstituting the solute contrast agent and filtering the reconstituted contrast agent solution. The filtration module 400 may be the same as or similar to the filtration module 400 described herein with reference to FIGS. 16A and 16B . However, it is contemplated that another suitable filter or filtration module may be used.

[0094] The distribution manifold 140 may be fluidly connected to one or more diluent tanks, such as the WFI tank 200, via a first valve 142a and configured to provide selective fluid communication between one or more of the container (pouch 300), the first syringe 120a, the diluent tanks (the one or more WFI tanks 200), and the filtration module 400. The one or more WFI tanks 200 may be fluidly connected to the first valve 142a via a main water tube 202. A branch water tube 204 may extend from the main water tube 202 upstream of the first valve 142a. The branch water tube 204 may be fluidly connected to a fourth valve 144, which may be located remotely from the distribution manifold 140. It should be noted that the branched water tube 204 and the fourth valve 144 are only required in embodiments of the system 1000 that include a pre-made liquid contrast injection source, and thus the branched water tube 204 and the fourth valve 144 need not be present in embodiments that use only dry contrast for injection. The pouch 300 may be received by the agitator 600.

[0095] The filtration module 400 may be fluidly connected to the first valve 142a via a filtration inlet tube 402 and to the fourth valve 144 via a first filtration outlet tube 404. The fourth valve 144 may also be fluidly connected to the second valve 142b via a second filtration outlet tube 406. One or more cleaning agent reservoirs 500 may be fluidly connected to the third valve 142c of the distribution manifold 140 via the cleaning agent tube 502.

[0096] In some embodiments, fourth valve 144 may be fluidly connected to liquid contrast reservoir 550 via bypass tubing 552. Liquid contrast reservoir 550 may contain contrast already in liquid form and may be used during an injection procedure as a supplement to, or in place of, the reconstitution contrast agent in pouch 300. In other embodiments, liquid contrast reservoir 550, bypass tubing 552, branch water line 204, and fourth valve 144 may be omitted, and first filtration outlet tube 404 may be connected to second valve 142b.

[0097] First valve 142a may facilitate selective fluid flow control from one or more of WFI reservoirs 200, pouch 300, and first syringe 120a. Second valve 142b may facilitate selective fluid flow control from second syringe 120b and second filtration outlet tube 406. Third valve 142c may be configured to provide selective fluid communication between third syringe 120c, administration line 510, and one or more cleaning agent reservoirs 500. Fourth valve 144 facilitates fluid flow from branch water line 204, first filtration outlet tube 404, second filtration outlet tubing 406, and bypass tubing 552.

[0098] The controller 900 may be configured to actuate the valves 142a, 142b, 142c, 144, the pistons 122a, 122b, 122c associated with the syringes 120a, 120b, 120c, and the agitator 600 in a predetermined sequence as shown in Figures 18 through 25 to reconstitute the solute contrast agent contained in the pouch 300 and ultimately deliver a dose to the patient.

[0099] 18 , diluent from one or more WFI baths 200 must first be injected into pouch 300. To that end, first valve 142a can be positioned to establish fluid communication between first syringe 120a and main water tubing 202. First piston 122a associated with first syringe 120a can be retracted proximally to draw fluid from one or more WFI baths 200 into first syringe 120a. Then, as shown in FIG. 19 , first valve 142a can be positioned to establish fluid communication between first syringe 120a and contrast tubing 206. First piston 122a can be advanced distally to inject fluid from one or more WFI baths 200 through contrast tubing 206 into pouch 300. When fluid is injected into pouch 300, the fluid mixes with and reconstitutes the solute contrast agent in pouch 300 to produce a liquid contrast agent. Agitator 600 may be activated during reconstitution of the contrast agent to agitate the pouch and increase the effectiveness of the reconstituted contrast agent.

[0100] Once the contrast agent in pouch 300 is reconstituted, first valve 142a is maintained in the same position as in FIG. 19 to maintain fluid communication between first syringe 120a and contrast agent tubing 206. Then, as shown in FIG. 20, piston 122a associated with first syringe 120a may be retracted to draw the reconstituted contrast agent from pouch 300 into first syringe 120a. At this stage, the reconstituted contrast agent may contain particulates and / or impurities, as described above, which are then removed by filtration. While filtration module 400 is described here in the context of a three-barrel configuration, typically positioned between first syringe 120a and second syringe 120b, this may not necessarily be the case in a two-barrel configuration, as described above.

[0101] 21 , once the reconstitution contrast agent has been loaded into first syringe 120a, first valve 142a may be positioned to establish fluid communication between first syringe 120a and filtration inlet tube 402. Fourth valve 144 may be positioned to establish fluid communication between first filtration outlet tube 404 and second filtration outlet tube 406. Second valve 142b may be positioned to establish fluid communication between second syringe 120a and second filtration outlet tube 406. In such a case, a fluid path may be formed from first syringe 120a through filtration module 400 to second syringe 120b. First piston 122a associated with first syringe 120a may be advanced to inject the reconstitution contrast agent in first syringe 120a through filtration module 400 toward second syringe 120b. Simultaneously with the injection of the reconstituted contrast agent from the first syringe 120a, the second piston 122b associated with the second syringe 120b can be retracted to draw the reconstituted contrast agent into the second syringe 120b. As the reconstituted contrast agent passes through the filtration module 400 on its way to the second syringe 120b, the filtration module 400 removes particulates and impurities from the reconstituted contrast agent. Thus, the reconstituted contrast agent loaded in the second syringe 120b is suitable for injection into the patient. The filtration process may take approximately one minute in some embodiments, but the filtration time is determined by the size and density of the filter material in the filtration module, along with other factors such as the flow rate of the reconstituted contrast agent through the filtration module. The filtration time is also predicted based on (i) the number of particulates in the pouch and (ii) the number of injection cycles the filtration module undergoes (e.g., injection n100 requires more time than injection n1 due to particulate accumulation in the filtration module).

[0102] To begin the injection procedure, second valve 142b is positioned to establish fluid communication with infusion set 510 via third valve 142c, as shown in FIG. 22. In such a case, advancement of second piston 122b associated with second syringe 120b may inject reconstruction contrast agent from second syringe 120b through second valve 142b, through third valve 142c, into infusion set 510, and ultimately into the patient. Additionally, this position of third valve 142c may also establish fluid communication between third syringe 120c and infusion set 510, allowing injection of a cleaning agent (e.g., saline) from third syringe 120c into the patient.

[0103] Referring to FIG. 23 , second syringe 120b is partially filled with unused contrast medium after an injection procedure. In such a case, second piston 122b is in an intermediate position within syringe 120b, and the volume between piston 122b and the distal end of syringe 120b is filled with unused contrast medium. As shown in FIG. 23 , first valve 142a is positioned to establish fluid communication between first syringe 120a and second valve 142b. Second valve 142b is positioned to establish fluid communication between second syringe 120b and first valve 142a. In such a case, a flow path is formed between first syringe 120a and second syringe 120b.

[0104] Referring now to FIG. 24, to inject unused contrast medium from second syringe 120b into first syringe 120a, first piston 122a is retracted while second piston 122b is advanced.

[0105] Referring now to FIG. 25 , first valve 142a is positioned to establish fluid communication between first syringe 120a and pouch 300. First piston 122a may then be advanced to inject unused contrast agent from first syringe 120a into pouch 300. Pouch 300 may then be disconnected from stirrer 600 and contrast agent line 206, as shown in FIGS. 29C and 30C . Pouch 300 filled with unused contrast agent may be sent and / or transported to an appropriate facility for recycling and / or regeneration. In particular, iodine and / or other active ingredients may be recovered from the unused contrast agent. This eliminates the need for hazardous disposal of unused contrast agent.

[0106] As described above with reference to the non-limiting embodiment of system 1000 having two barrels, the actuation of valves 142a, 142b, 142c, 144 and the advancement / retraction of pistons 122a, 122b, 122c to the various positions shown in Figures 18-25 may be performed automatically by controller 900 according to a pre-programmed injection procedure. Thus, controller 900 may be programmed or configured to deliver reconstituted contrast agent solution from a container (e.g., pouch 300) to first syringe 120a, from first syringe 120a to filtration module 400, from filtration module 400 to second syringe 120b, and from second syringe 120b to administration line 510. Additionally, controller 900 may be programmed or configured to deliver cleaning agent from cleaning agent reservoir 500 into third syringe 120c and to deliver cleaning agent from third syringe 120c to administration line 510.

[0107] Having outlined the process of reconstituting and injecting contrast agent from pouch 300, further details of a suitable container for containing and reconstituting a solute contrast agent, such as pouch 300, will now be described. Referring to FIGS. 26A through 27C, pouch 300 may include a flexible membrane including upper and lower membranes 302 and 304 joined by a perimeter seam 306. Membranes 302, 304 may be sized to contain a predetermined amount of dry contrast agent between them. In some embodiments, pouch 300 may be configured to contain between about 61.3 grams and about 63.3 grams of dry contrast agent, and membranes 302, 304 may have a length and width of about 120 mm and 85 mm, respectively, in the area bounded by perimeter seam 306. The amount of dry contrast agent contained within pouch 300 between membranes 302, 304 may be selected to be approximately equivalent to a standard dose of a conventional liquid contrast agent. For example, 62.3 grams of dry contrast agent, when reconstituted, can produce a dose approximately equivalent to 100 milliliters of a conventional liquid contrast agent. Powder formulations are designed so that the reconstituted contrast agents of the present disclosure are equivalent to approved indications.

[0108] When pouch 300 is empty, membranes 302, 304 may lie substantially flush with one another so that pouch 300 defines a negligible interior volume, as shown in Figures 26A and 27A. Flexible membranes, including membranes 302, 304, may be flexible, stretchable, and configured to expand when pouch 300 is filled with dry contrast agent and fluid, such that membranes 302, 304 stretch and provide an interior volume for reconstituted contrast agent. Membranes 302, 304 may also be elastic so that membranes 302, 304 return to the unstretched state of Figure 27A after contrast agent is withdrawn from pouch 300.

[0109] An internal valve 310 may be provided within the pouch 300 and configured to receive a spike of the contrast line to allow flow into and out of the interior volume between the membranes 302, 304, thereby fluidly communicating with the first valve 142a upon placement of the container within the fluid injector system 1000. In some embodiments, as shown in FIG. 28 , the internal valve 310 defines an orifice 308 through which the spike can be inserted. In some embodiments, the internal valve 310 may be a film valve including opposing film portions 314, 316 that can be separated by the spike to access the interior volume of the pouch 300 between the membranes 302, 304. The internal valve 310 may further be configured to passively seal the container when the spike is removed from the internal valve 310.

[0110] 27A, the upper membrane 302 and / or the lower membrane 304 may include a readable solute contrast agent identifier, such as an identification indicia 312. The identification indicia 312 may be a barcode, QR code, RFID tag, text, symbol, etc. that the controller 900 or operator can use to verify that the correct approved pouch 300 has been connected before initiating reconstitution and patient injection.

[0111] The pouch 300 may be filled with a dry contrast agent as part of the manufacturing process. Any type of dry contrast agent suitable for reconstitution may be contained in the pouch. In one example, the dry contrast agent includes iopromide as the sole active ingredient. In addition to the active ingredient, the dry contrast agent may include a complexing agent, a buffering agent, a pH adjusting agent, and combinations thereof. An example of a complexing agent may include edetate calcium sodium. An example of a buffering agent may include trometamol. An example of a pH adjusting agent may include a dry powder equivalent to hydrochloric acid (e.g., 10% hydrochloric acid), which is used to maintain a near-neutral pH of the contrast agent. The amount of each component may be configured to match the amount of components of a conventional liquefied contrast agent, taking into account the WFI added to the dry contrast agent during reconstitution. Other examples of suitable dry contrast agents include, but are not limited to, iohexol (trade name Omnipaque™), iopamidol (trade name Isovue®), iomeprol (trade name Iomeron®), ioversol (trade name Optiray®), iobitridol (trade name Xenetix®), or iodixanol (trade name Visipaque™).

[0112] The pouch 300 may be sterilized prior to use in the system 1000 to kill contaminants, such as viruses, bacteria, and other germs, present in the dried contrast agent. In some non-limiting embodiments, the killed contaminants may then be filtered out by a filter, such as a filtration module 400 (see, e.g., FIGS. 15-22 ), to prevent accidental injection into a patient. However, as previously suggested, filtration and / or the filtration module 400 may not be required if the solute contrast agent contained in the container undergoes high-temperature sterilization and / or depyrogenation before entering the system 1000. Sterilization of the pouch 300 may include electron beam irradiation, gamma irradiation, low-temperature dry heat sterilization processes, and combinations thereof. Sterilization may be performed on the pouch 300 individually or on a package containing multiple pouches 300. The membranes 302, 304 must be made of a material that can withstand the sterilization process without degradation. For example, the flexible membrane and membranes 302, 304 may be made of a polymer, such as a recyclable plastic. The use of recyclable plastic also allows the pouch 300 to be recycled after use through conventional channels that do not involve the handling of hazardous materials.

[0113] In some non-limiting embodiments, the material may be constructed from polyethylene terephthalate (PET) or polyetheretherketone (PEEK) to facilitate the application of high-temperature, dry-heat sterilization so that the solute contrast agent is depyrogenated. Other suitable polymeric materials may also be utilized, so long as they are capable of adequately withstanding the high-temperature, dry-heat sterilization conditions for sterilization of the pouch and its contents, and avoid significant degradation after exposure to sterilization heat for the sterilization time period employed.

[0114] In some non-limiting embodiments, the application of high-temperature dry heat sterilization eliminates the need to filter the reconstituted contrast agent solution using, for example, filtration module 400. High-temperature dry heat sterilization involves heating container (pouch) 300 and its contents to at least 150°C, ideally 200°C or above. The dry heat is applied to the container and its contents for a preselected dry heat sterilization period (e.g., 1 hour, 1.5 hours, etc.) to sterilize the solute contrast agent contained within container 300. This sterilization process can sterilize the solute contrast agent and container 300 so that contaminants such as viruses, bacteria, or other pathogens are destroyed. When high-temperature dry heat sterilization is applied, it is believed that the reconstituted contrast agent can be passed for infusion into a patient without the use of filtration, as the higher temperature decomposes endotoxins and forms pyrogen-free material. The higher temperatures required to decompose endotoxins are 200°C or above. Thus, the container or pouch 300 may be heat treated to cause the solute contrast agent to reach a temperature of at least 150°C and to sterilize the solute contrast agent, or preferably to reach a temperature of at least 200°C, so that the solute contrast agent is purified by depyrogenation.

[0115] Alternatively, filtration module 400 may be used during the infusion process that utilizes only coarse particle filtration (e.g., removal of larger particulates) or another type of filter or filtration module configured to remove particulates between 0.22 microns or 0.22 microns and 0.10 microns (e.g., filtration to remove endotoxins and killed bacteria can be removed through filtration that may be approximately 0.22 microns in size). It is possible that killed viruses, which may be too small to filter, may enter the patient as killed viruses through the infusion. Even if this occurs, this is not believed to pose a significant health risk to the patient because the viruses are killed.

[0116] Thus, there are a variety of methods related to the present disclosure and the manufacture and preparation of container 300 for use with a fluid injector system, and solute contrast agent sealed within container 300. The preparation of the solute contrast agent and container 300 may, in part, determine the method of reconstitution.

[0117] In some non-limiting embodiments, a method involving the use of a solute contrast agent with possible or uncertain endotoxin content includes filling a container 300 (e.g., a pouch) with the solute contrast agent, heating the container 300 with the solute contrast agent therein to a temperature of at least 150°C, reconstituting the solute contrast agent with WFI to form a reconstituted contrast agent solution, and filtering the reconstituted contrast agent solution to remove coarse particles through a filter designed to capture particles 10-20 microns or larger, or smaller particles through a small-pore filter designed to capture particles larger than a predetermined size (e.g., 0.2 mm), optionally assisted by the use of an auxiliary pump to help push the solution through the small-pore filter. The filter used in this filtration step is intended to remove particulates, endotoxins, bacteria, viruses, etc., from the reconstituted contrast agent solution.

[0118] In other non-limiting embodiments, a method involving the use of a solute contrast agent with possible or suspected endotoxin may include filling a container 300 (e.g., a pouch) with the solute contrast agent, heating the container 300 with the solute contrast agent therein to a temperature of at least 200°C for a preselected dry heat sterilization time, and reconstituting the solute contrast agent with WFI to form a reconstituted contrast agent solution. The method does not require the use of a filter, as higher temperatures (i.e., 200°C or higher) will kill bacteria, viruses, and other pathogens and decompose endotoxins released therefrom, resulting in a pyrogen-free material.

[0119] In another non-limiting embodiment, a method including producing a solute contrast agent as a non-pyrogenic (endotoxin-free) powder sealed in a container in a sterile environment includes the steps of: preparing a sterile environment; producing the solute contrast agent in the sterile environment such that the solute contrast agent is produced as a non-pyrogenic (endotoxin-free) powder; and aseptically filling the non-pyrogenic (endotoxin-free) powder into a container 300 in the sterile environment, thereby producing a pre-sterilized pouch containing the pre-sterilized solute contrast agent, such that the pre-sterilized pouch is ready for use with the methods and fluid injector systems of the present disclosure without the need for the heating and filtering steps required in other non-limiting embodiments.

[0120] After sterilization, the sterilized pouches can be placed in a box or other container for transport to a care facility. Alternatively, the pouches can be placed in a package or box and then subjected to dry heat sterilization for a preselected sterilization time to sterilize the pouches before the box is transported to the care facility.

[0121] Use of system 1000 to reconstitute the contents of a container such as pouch 300 can result in significant sustainability improvements, including increased packaging efficiency, significant reductions in emissions and energy consumption, and component recyclability. For example, pouch 300 allows for larger doses to be shipped and stored in the same volume of packaging as conventional liquid contrast media. Pouches also require less energy to manufacture than conventional contrast media tanks. Therefore, CO2 emissions, manufacturing energy, transport mass, and transport volume are all reduced, reducing environmental impact and cost. Pouches are fully recyclable through conventional recycling streams, and solutes such as iodine can be recovered from unused contrast media. Thus, there are significant improvements related to cost and environmental impact resulting from the implementation of system 1000 and the related devices and methods described herein.

[0122] 28, once sterilized (and / or cleaned through depyrogenation) and removed from any packaging, pouch 300 can be connected to contrast tube 206. Contrast tube 206 can include spike 320 for connecting to internal valve 310 of pouch 300. To connect pouch 300 to contrast tube 206, spike 320 can be inserted into valve 310 along direction A to open orifice 308 and establish fluid communication between contrast tube 206 and the interior of pouch 300 containing the dried contrast agent. Once this connection is made, the dried contrast agent can be reconstituted by injecting fluid through contrast tube 206 into pouch 300 along direction B, as shown in FIG. 29A. This injection can be accomplished by appropriate actuation of first valve 142a and piston 122a (shown in FIGS. 3 and 19). As shown in Figure 29B, reconstituted liquid contrast can be drawn from pouch 300 through contrast tube 206 by creating a vacuum along direction C, such as by retracting piston 122a (shown in Figures 4 and 20). Figure 29C illustrates disconnection of pouch 300 from contrast line 206. Spike 320 is withdrawn from valve 310 along direction D, and simultaneously, a vacuum is applied to contrast tube 206 along direction C (e.g., by retracting piston 122a in Figure 4) to reseal internal valve 310 while ensuring that contaminants do not enter.

[0123] 30A-30C, further details of spike 320 are shown being inserted into and removed from pouch 300. Referring first to FIG. 30A, valve 310 can include an upper film 314 and a lower film 316 that are spread apart by spike 320 to define an internal conduit 318. With spike 320 fully inserted into internal valve 310, internal conduit 318 extends into the internal cavity of pouch 300, as shown in FIG. 29A, allowing fluid to flow from spike 320 to pouch 300 and vice versa. Referring now to FIG. 30B, with spike 320 partially inserted into (or partially removed from) internal valve 310, upper film 314 and lower film 316 passively relax toward each other, reducing the cross-sectional area of ​​internal conduit 318. At a particular insertion depth of spike 320, top film 314 and bottom film 316 relax such that top film 314 meets bottom film 316 at point 319, as shown in Figure 29C. At point 319, internal conduit 318 closes to prevent fluid from entering or leaving internal valve 310, as shown in Figure 30C. The passive seal formed at point 319 allows spike 320 to be completely removed without leaking the contents of pouch 300 and without allowing contaminants from the environment to enter pouch 300.

[0124] 31A and 31B, non-limiting embodiments of a distribution manifold 140 of a system 1000 are shown in detail. FIG. 31A illustrates an exemplary distribution manifold 140 configured for a two-barrel configuration of a system 1000, such as the system 1000 illustrated in FIGS. 1-9. FIG. 31B illustrates an exemplary distribution manifold 140 configured for a three-barrel configuration of a system 1000, such as the system 1000 illustrated in FIGS. 17-25. The distribution manifold 140 can have various ports and features depending on the embodiment or configuration of the system 1000. In some non-limiting embodiments, the distribution manifold 140 includes a body 143 to which valves 142a, 142b, etc., are connected via valve seats 132a, 132b, etc. The distribution manifold 140 can include a contrast port 150, a WFI port 152, an irrigant port 158, and an infusion port 160 configured to connect to an infusion set, such as an administration line 510. The distribution manifold 140 may further include conduits, such as a first manifold conduit 170, for fluidly connecting the valves 142a, 142b, etc. and the ports 150, 152, 158, 160, etc. in the distribution manifold 140.

[0125] 31A, distribution manifold 140 may further include air detection windows 190a-190c that allow various sensors to detect various characteristics of the fluid, such as the presence of air, as the fluid enters or leaves distribution manifold 140. As further shown in FIG. 31A, first manifold conduit 170 may fluidly connect first valve 142a and second valve 142b to each other as well as fluidly connect valves 142a, 142b to drip port 160, such that fluid passing from first syringe 120a through first valve 142a does not have to pass through second valve 142b, and fluid passing from second syringe 120b through second valve 142b does not have to pass through first valve 142a to reach drip port 160. Valves 142a, 142b may be, for example, stopcocks 142 that can be rotated to change which of ports 150, 152, 158, 160 and / or first conduit 170 are in fluid communication with syringes 120a, 120b and / or drip set 510.

[0126] 31B, distribution manifold 140 may further include a filtered inlet port 154 and a filtered outlet port 156 to enable filtration as described with reference to FIG. 21. As shown in FIG. 31B, first manifold conduit 170 fluidly connects first valve 142a to second valve 142b, and second manifold conduit 172 fluidly connects second valve 142b to third valve 142c and thus to drip port 160. Valves 142a through 142c may be stopcocks 142 that can be rotated to change which of ports 150, 152, 154, 156, 158, 160 and / or first and second conduits 170, 172 are in fluid communication with syringes 120a through 120c and / or drip set 510, for example.

[0127] Valves 142a, 142b, 142c may be rotated by controller 900 to various positions, such as those shown in Figures 1-9 and 17-25, to direct fluid communication between syringes 120a-120c, ports 150, 152, 154, 156, 158, 160, and first and second manifold conduits 170, 172. A non-limiting embodiment of a stopcock 142 according to the present disclosure is shown in Figures 32A and 32B. Stopcock 142 may include a fluid passage 146 and a fluid channel 148. Changing the direction and orientation of fluid passage 146 may control which components of system 1000 are fluidly connected. The stopcock 142 may further include a stopcock drive engagement portion 132, which allows the system 1000 and controller 900 to apply force through a motor or other similar mechanism to change the direction of the fluid passage 146 and therefore the fluid connections of the various components of the system 1000.

[0128] 33A through 37B, the agitator 600 includes a base 602 that is attached to the housing 110 or stand 112 of the fluid injector system 1000 via a bracket 604. The agitator 600 further includes a moving plate 610 to which the pouch 300 is removably attached. The moving plate 610 is configured with at least one degree of freedom, in which case it can translate along a plane and / or rotate about an axis. In some non-limiting embodiments, the plate 610 rotates about an axis perpendicular to the plate 610 and translates along a plane parallel to the plate 610. For example, the plate 610 can be agitated by rotation, oscillation, pivoting, linear actuation, and / or other motion. In some non-limiting embodiments, a motor 620 (e.g., a servo motor) is attached to the base 602 and connected to the moving plate 610 via a drive mechanism 622 coupled to the shaft of the base 602. Motor 620 may be driven by controller 900 (see FIGS. 11-14 ), which may be located within housing 110. As motor 620 rotates, drive mechanism 622 and plate 610 rotate. The rotational motion imparted to plate 610, in this case, and ultimately pouch 300, may facilitate reconstitution of the dried contrast agent and enhance uniformity of the reconstituted contrast agent. In some embodiments, motor 620 may be driven to rotate plate 610 at a rotational speed ranging from about 1000 rpm to about 3000 rpm. In some embodiments, agitator 600 may be operated for about two minutes to fully reconstitute pouch 300, which initially contains 62.3 grams of dried contrast agent.

[0129] In some non-limiting embodiments, the agitator 600 can include at least one heating element configured to apply heat to the container 300, the solute contrast agent, and the diluent contained therein during reconstitution. For example, an electrical heating mechanism can heat the plate 610 to aid in improved mixing (e.g., by accelerating the reconstitution process and / or improving the dissolution of the dry contrast agent in the diluent / WFI to reconstitute the contrast agent). In some non-limiting embodiments, the drive mechanism 622 can be a heating element. Heating can be achieved through conduction to heat the plate 610 to a preselected reconstitution temperature by thermal conduction between the heated plate 610 and the material in the container while agitation is occurring for reconstitution.

[0130] 33A through 33D, plate 610 may include an attachment mechanism for automatically connecting spike 320 of contrast tube 206 to pouch 300 in the manner shown in FIGS. 29A through 30C. The attachment mechanism may include a rail 640 attached to plate 610 and a carriage 650 slidable on rail 640. Carriage 650 may include a clip 652 or other retention member secured to spike 320. In preparation for a reconstitution procedure, carriage 650 may be advanced on rail 640 toward pouch 300 until spike 320 is fully seated in internal valve 310 of pouch 300, as shown in FIG. 33D. Carriage 650 may be automatically controlled by controller 900. The agitator 600 may be provided in an enclosure, such as covered by a lid 114 within the housing 110, as shown in Figures 13A-13B, to protect the agitator 600 and pouch 300 during the reconstitution and / or injection procedure.

[0131] FIGS. 34 through 37B show alternative embodiments of the agitator 600. In these embodiments, the agitator components are substantially similar to the embodiment of FIGS. 33A through 33D , and like numerals are used to indicate like components. As shown in FIGS. 34 through 35B , the plate 610 may include one or more clips 614 or other connecting features for securing the pouch 300 to the plate 610. In some embodiments, as shown in FIGS. 35A through 37B , the plate 610 may include a weight 612 to balance the weight of the pouch 300, thereby reducing vibrations transmitted to the base 602 and ultimately the housing 110 and stand 112 as the plate 610 moves. In some embodiments, the drive member 622 may also impart lateral movement to the plate 610. One example is shown in FIG. 36 , where the drive mechanism includes a channel 624 through which the plate's retaining pin 616 can slide. As the drive mechanism 622 rotates, the retaining pin 616 slides along the channel 624. Channel 624 may be of a particular profile, such as a dog leg, to impart a predetermined lateral movement to plate 610. In some embodiments, channel 624 may be configured to allow lateral movement of about 5 mm to about 10 mm, and in certain embodiments, about 9 mm. It should be understood that in other embodiments, channel 624 may be provided on the underside of plate 610, with retaining pin 616 extending upward from drive mechanism 622 to achieve substantially the same lateral movement profile of plate 610.

[0132] 37A and 37B, in some embodiments, the agitator 600 can include a rotating counterweight 630 configured to counteract vibrations caused by movement of the plate 610. The counterweight 630 can be coupled to the shaft of the motor 620 and can rotate about a rotational axis RA that is coaxial with the rotational axis of the motor 620. The rotating counterweight 630 can include a pin 632 offset from the rotational axis RA. The pin 622 is connected to a drive mechanism 622 and can rotate the drive mechanism 622 eccentrically relative to the motor 620. This eccentric rotation can then be imparted to the movable plate 610, resulting in lateral movement of the plate 610.

[0133] 38 through 46, FIG. 38 is a schematic diagram illustrating a non-limiting embodiment of a preset disclosed fluid injector system 1000 in a three-barrel configuration. In the illustrated embodiment, the components of system 1000 are substantially similar to the embodiment of FIGS. 1 through 9, and like numerals are used to indicate like components. As shown in the illustrated embodiment, system 1000 may include a third syringe 120c and a corresponding third valve 142c such that system 1000 includes three syringes 120a, 120b, 120c fluidly connected to a distribution manifold 140. In this exemplary three-barrel embodiment, third valve 142c may be configured to provide fluid communication between third syringe 120c, liquid contrast reservoir 550, and one or more of administration line 510. Accordingly, the flow control assembly may include distribution manifold 140 that may be fluidly connected to bypass tubing 552 and liquid contrast reservoir 550 via third valve 142c.

[0134] In some embodiments, the liquid contrast reservoir 550 may already contain a contrast agent in liquid form and may be used during an injection procedure as a supplement to, or in place of, the reconstituted contrast agent in the pouch 300. The liquid contrast agent may also be an injectable reconstituted contrast agent solution previously produced by the system 1000. The use of a supplemental liquid contrast agent may be necessary, for example, due to a patient allergy or the potential unavailability of a pouch 300 containing a solute contrast agent. In other embodiments, the liquid contrast reservoir 550 may be used for a recycling or regeneration process related to the reconstituted contrast agent solution. In other embodiments, as shown in FIGS. 1 through 9, the liquid contrast reservoir 550 and bypass tubing 552 may be omitted.

[0135] 38-46, in which pouch 300 is provided and reconstitution of the solute contrast agent within pouch 300 is shown, system 1000 operates as shown in FIGS. 1-9, with third valve 142c closed to prevent flow to and from liquid contrast reservoir 550 and third syringe 120c unless or until its use is desired for recycling / regeneration. If an unused portion of the injectable reconstituted contrast agent solution from pouch 300 remains in first syringe 120a, controller 900 may be programmed or configured to deliver the unused portion of the injectable reconstituted contrast agent solution from first syringe 120a to third syringe 120c and from third syringe 120c to liquid contrast reservoir 550.

[0136] First valve 142a may facilitate selective fluid flow control between one or more of WFI reservoirs 200, pouch 300, first syringe 120a, and administration line 510. Second valve 142b may facilitate selective fluid flow control between one or more of second syringe 120b, one or more cleaning agent reservoirs 500, and administration line 510. Third valve 142c may be configured to provide selective fluid communication between one or more of third syringe 120c, liquid contrast agent reservoir 550, and administration line 510.

[0137] The controller 900 may be configured to actuate the valves 142a, 142b, 142c and the pistons 122a, 122b, 122c associated with the syringes 120a, 120b, 120c in a predetermined sequence as shown in Figures 39 through 42 to deliver the liquid contrast agent from the liquid contrast agent reservoir 550 to the administration line 510 and ultimately to the patient.

[0138] 39 , liquid contrast from liquid contrast reservoir 550 must first be injected into pouch 300. To that end, third valve 142c can be positioned to establish fluid communication between third syringe 120c and bypass tubing 552. Third piston 122c associated with third syringe 120c can be retracted proximally to draw liquid contrast from liquid contrast reservoir 550 into third syringe 120c, as shown in FIG. 39 . Simultaneously, second valve 142b can be positioned to establish fluid communication between second syringe 120b and irrigant tubing 502. Second piston 122b associated with second syringe 120b can be retracted proximally to draw irrigant into second syringe 120b, as shown in FIG. 39 . Because pouch 300 is not utilized in the illustrative example, first valve 142a is closed and first piston 122a is not actuated. As shown in Figure 40, second piston 122b and third piston 122c can be advanced distally to deliver the flushing agent (e.g., saline) from second syringe 120b and the liquid contrast agent from third syringe 120c into administration line 510 and the patient.

[0139] It is contemplated that a filter, such as filtration module 400, and / or a pump, such as pump 450, may be included in bypass tube 502 to filter the liquid contrast agent before it enters third syringe 120c. The application of filtration module 400 and / or pump 450 is the same as or similar to that applied to contrast agent tube 206, as shown and described with reference to FIG. 15 . It is also contemplated that the liquid contrast agent will be free of particulates and / or impurities that require filtration by system 1000, because the liquid contrast agent may have already been filtered and / or depyrogenated prior to the reconstruction previously performed by system 1000.

[0140] 41, third syringe 120c is partially filled with unused contrast agent after the injection procedure. Thus, third piston 122c is in an intermediate position within third syringe 120c, and the volume between piston 122c and the distal end of syringe 120c is filled with unused contrast agent. As shown in FIG. 41, third valve 142c is positioned to establish fluid communication between third syringe 120c and liquid contrast agent reservoir 550.

[0141] Referring now to FIG. 42, third piston 122c is advanced to deliver unused liquid contrast to liquid contrast reservoir 550 for recycling and / or regeneration procedures.

[0142] In a triple-barrel embodiment in which solute contrast agent from pouch 300 is reconstituted and the reconstituted contrast agent solution is delivered to the patient, first syringe 120a may be partially filled with unused injectable reconstituted contrast agent solution, as shown in FIG. 43. Thus, first piston 122a is in an intermediate position within first syringe 120a, and the volume between piston 122a and the distal end of syringe 120a is filled with unused contrast agent. As shown in FIG. 44, first valve 142a is positioned to establish fluid communication between third syringe 120c and pouch 300. First piston 122a is then advanced to inject unused contrast agent from first syringe 120a into pouch 300 for recycling and / or regeneration.

[0143] A method for reconstituting and injecting a contrast agent in the fluid injector system of the illustrated embodiment may include fluidly connecting a diluent reservoir 200 containing a diluent to a first syringe 120a, fluidly connecting a cleaning agent reservoir 500 containing a cleaning agent to a second syringe 120b, fluidly connecting a container 300 containing a solute contrast agent to the first syringe 120a, and fluidly connecting a liquid contrast agent reservoir 550 containing a liquid contrast agent to a third syringe 120c. The method may further include the steps of delivering a cleaning agent from the cleaning agent reservoir 500 into the second syringe 120b, delivering the cleaning agent from the second syringe 120b into the administration line, delivering a liquid contrast agent from the liquid contrast agent reservoir 550 into the third syringe 120c, and delivering the liquid contrast agent from the third syringe 120c into the administration line.

[0144] Referring now to FIG. 25 , first valve 142a is positioned to establish fluid communication between first syringe 120a and pouch 300. First piston 122a may then be advanced to inject unused contrast agent from first syringe 120a into pouch 300. Pouch 300 may then be disconnected from stirrer 600 and contrast agent line 206, as shown in FIGS. 29C and 30C . Pouch 300 filled with unused contrast agent may be sent and / or transported to an appropriate facility for recycling and / or regeneration. In particular, iodine and / or other active ingredients may be recovered from the unused contrast agent. This eliminates the need for hazardous disposal of unused contrast agent.

[0145] It should be noted that prior to connecting pouch 300 to contrast tubing 206 and / or attaching liquid contrast reservoir 550 to bypass tubing 552, system 1000 is purged and primed to prevent air from being accidentally injected into the patient. Referring now to FIGS. 45 and 46, the air purging operation of system 1000 is initiated by retracting each of pistons 122a, 122b, 122c as shown in FIG. 45. First valve 142a is positioned to establish fluid communication between first syringe 120a and contrast tubing 206. Second valve 142b is positioned to establish fluid communication between second syringe 120b and infusion set 510. Third valve 142c is positioned to establish fluid communication between third syringe 120c and bypass tubing 552. 46, pistons 122a, 122b, 122c may be advanced to expel air from syringes 120a, 120b, 120c. In some embodiments, particularly if syringes 120a-120c are part of a "day set," the air purge procedure is performed only once per day after the "day set" is initially connected to system 1000. Subsequent injections from the same "day set" do not require air purging. Note that during the air purge operation, pouch 300 is not connected to contrast tubing 206, and liquid contrast reservoir 550 is not connected to bypass tubing 552, because purged air must be able to escape from system 1000 through contrast tubing 206, bypass tubing 552, and / or infusion set 510. Similar air purging operations are performed by other embodiments of the system 1000 described herein, with components included in the system determining the position of valves 142a, 142b, etc. to allow fluid connection of syringes 120a, 120b, etc. to an environment external to the system 1000 so that air can be purged from the system 1000.

[0146] 47 and 48, which illustrate a system 1000 performing a priming operation as shown and described with reference to FIGS. 1-9. As shown in FIG. 47, the priming operation may be initiated by positioning valves 142a, 142a to draw a diluent, such as WFI, from diluent reservoir 200 and / or a cleaning agent from cleaning agent reservoir 500 into syringes 120a, 120b. As shown in FIG. 47, first valve 142a is positioned to establish fluid communication between first syringe 120a and one or more WFI reservoirs 200. Second valve 142b is positioned to establish fluid communication between second syringe 120b and one or more cleaning agent reservoirs 500. As shown in FIG. 47, the first piston 122a is retracted to draw fluid from one or more WFI reservoirs 200 into the first syringe 120a, and the second piston 122b is retracted to draw fluid from one or more cleaning agent reservoirs 500 into the second syringe 120c.

[0147] 48, first valve 142a is then positioned to establish a fluid connection between first syringe 120a, which is filled with fluid from one or more WFI reservoirs 200, and contrast tubing 206. Piston 122a is then advanced to inject a portion of the fluid from first syringe 120a through contrast tubing 206, thereby priming contrast tubing 206 with WFI fluid. At this point, contrast tubing 206 is suitable for connection to pouch 300. Infusion set 510 is then primed with cleaning agent drawn from one or more cleaning agent reservoirs 500. Second valve 142b is positioned to establish fluid communication between second syringe 120b, which is pre-filled with cleaning agent, and infusion set 510. Piston 122c is advanced to inject cleaning agent from second syringe 120b through infusion set 510. The infusion set 510 is now primed and suitable for connection to a patient's vein. Similar air purging operations are performed by other embodiments of the system 1000 described herein, including components that position valves 142a, 142b, etc. to allow fluid connection of syringes 120a, 120b, etc. to prime various components of the system 1000 with diluent and / or flushing agent.

[0148] 49, which is a sequence diagram illustrating a method 1100 of reconstituting a solute contrast agent and injecting the reconstituted contrast agent solution into the fluid injector system 1000. The method 1100 may include fluidly connecting a diluent reservoir 200 containing a diluent, such as WFI, to a first syringe 120a, as shown in step 1102.

[0149] 1-9 , method 1100 may include fluidly connecting a cleaning agent reservoir 500 to second syringe 120b in step 1103. If step 1103 is included in method 1100, the method may further include delivering cleaning agent from cleaning agent reservoir 500 into second syringe 120b and delivering cleaning agent from second syringe 120b into dispensing line 510 of fluid injector system 1000.

[0150] Further, the method may optionally include purging system 1000 of air in step 1105a before fluidly connecting container 300 to first syringe 120a, as described with reference to FIGS. 45 and 46. The method may also include priming the system with diluent from diluent reservoir 200 and cleaning agent from cleaning agent reservoir 500 in step 1105b, as described with reference to FIGS. 47-48. Step 1105b may be performed after fluidly connecting cleaning agent reservoir 500 to second syringe 120b and before connecting container 300 containing solute contrast agent to first syringe 120a of fluid injector system 1000. Method 1100 may also include method 1200 for approving components for use with system 1000, as shown and described below with reference to FIG.

[0151] In step 1104, the method 1100 may further include fluidly connecting a container 300 containing the solute contrast agent to the first syringe 120a. Then, in step 1106, a diluent may be drawn from the diluent reservoir 200 into the first syringe 120a and delivered from the first syringe 120a to the container 300 for reconstitution of the solute contrast agent. Then, in step 1108, the container 300 may be agitated to reconstitute the solid contrast agent into a reconstituted contrast agent solution.

[0152] In some non-limiting embodiments, the container 300 may also be heated for reconstitution, as shown in step 1109 .

[0153] In some non-limiting embodiments, after reconstitution, the reconstituted contrast agent solution may optionally be filtered, as shown in step 1111. In step 1111, method 1100 may include purifying the reconstituted contrast agent solution by passing it through a filter, such as filtration module 400 comprising at least one filter medium, before delivering the reconstituted contrast agent solution into administration line 510 of fluid injector system 1000.

[0154] 49 , as shown in step 1112, the reconstituted contrast agent solution may be delivered from container 300 into first syringe 120a. Method 1100 may then include, in step 1114, delivering the injectable reconstituted contrast agent solution from first syringe 120a into administration line 510. In step 1116, the reconstituted contrast agent solution and / or the cleaning agent may be administered to the patient.

[0155] In some non-limiting embodiments, after injection, unused reconstituted contrast agent may be reused in optional step 1117 by delivering an unused portion of the reconstituted contrast agent solution from first syringe 120a into container 300. Alternatively, unused reconstituted contrast agent may be reused in optional step 1117 by delivering an unused portion of the reconstituted contrast agent solution from first syringe 120a into liquid contrast agent reservoir 550.

[0156] In some non-limiting embodiments, the method of reconstituting a solute contrast agent and injecting the reconstituted contrast agent solution into the fluid injector system 1000 may further include removing the container 300 or liquid contrast agent reservoir 550 containing the unused portion of the injectable reconstituted contrast agent solution from the fluid injector system and sending the container 300 or liquid contrast agent reservoir 550 to a recycling facility to recover the active components of the reconstituted contrast agent solution. Additionally or alternatively, the liquid contrast agent reservoir 550 without the unused reconstituted contrast agent solution may be stored for use in a later injection procedure.

[0157] In some non-limiting embodiments, the method of reconstituting a solute contrast agent and injecting the reconstituted contrast agent solution into the fluid injector system 1000 may further include sterilizing the contrast agent by heating the solute contrast agent in the container 300 to a temperature of at least 150°C before fluidly connecting the container 300 to the first syringe 120a.

[0158] 14 and 27A, the pouch 300 may include at least one indicia, such as a readable irrigant identifier 312, which the controller 900 may use to verify the injection procedure. The one or more WFI reservoirs 200 and the one or more irrigant reservoirs 500 may also include similar indicia. Thus, the irrigant reservoirs 500 may include at least one readable irrigant identifier, and the diluent reservoirs 200 may include at least one readable diluent identifier. Additionally, the system 1000 may include at least one reader or sensor configured to scan and read the at least one readable solute contrast agent identifier, the at least one readable irrigant identifier, and the at least one readable diluent identifier and communicate the identifier information with the controller 900.

[0159] The reader may be part of or in communication with the controller 900 when an operator prepares the system 1000 for use. The controller 900 may be further programmed or configured to process the identifier information and, based on the identifier information, start and stop fluid communication between one or more of the diluent reservoir 200, the container 300, the first syringe 120a, and the dispensing line 510, and between one or more of the cleaning agent reservoir 500, the second syringe 120b, and the dispensing line 520.

[0160] 50 is a sequence diagram illustrating a method 1200 for verifying the connection of a pouch 300, one or more WFI tanks 200, and one or more cleaning agent tanks 500. In step 1202 of method 1200, a readable diluent identifier of a WFI tank 200 is scanned by a reader. From the indicia, controller 900 verifies that one or more WFI tanks 200 are coupled to system 1000, and controller 900 may further ascertain information about the one or more WFI tanks 200, such as the type and amount of liquid contained in the one or more WFI tanks 200.

[0161] 50, in step 1204 of method 1200, one or more WFI vessels 200 are attached to the housing 110 and / or stand 112 (shown in FIGS. 13A, 13B, and 34) by an operator. In some embodiments, the housing 110 and / or stand 112 may include an arm from which the one or more WFI vessels 200 are suspended. In some embodiments, the arm may automatically extend from the housing 110 and / or stand 112 upon scanning the diluent identifier in step 1202. The operator may then connect the water tubing 202 to the WFI port 152 of the distribution manifold 140 (shown in FIGS. 31A and 31B) to establish fluid communication between the one or more WFI vessels 200 and the first valve 142a.

[0162] 50 , in step 1206 of method 1200, the readable detergent identifier of the detergent reservoir 500 is scanned by a reader. From the readable detergent identifier, the controller 900 determines that one or more detergent reservoirs 500 are coupled to the system 1000, and the controller 900 may further determine information about the one or more detergent reservoirs 500, such as the type and amount of liquid contained in the one or more detergent reservoirs 500.

[0163] 50, in step 1208 of method 1200, one or more cleaning agent reservoirs 500 are attached to housing 110 and / or stand 112 (shown in FIG. 11) by an operator. In some embodiments, housing 110 and / or stand 112 include arms from which one or more cleaning agent reservoirs 500 are suspended. In some embodiments, the arms may automatically extend from housing 110 and / or stand 112 upon scanning a readable cleaning agent identifier in step 1206. The operator may then connect cleaning agent tubing 502 to cleaning agent port 158 ​​of distribution manifold 140 (shown in FIGS. 31A and 31B) to establish fluid communication between one or more cleaning agent reservoirs 500 and third valve 142c.

[0164] 50 , in step 1210 of method 1200, the readable contrast agent identifier 312 of pouch 300 is scanned by a reader. From the readable contrast agent identifier 312 of pouch 300, controller 900 determines that pouch 300 should be coupled to system 1000, and controller 900 may further determine information about pouch 300, such as the type and amount of dry contrast agent contained therein, the expiration date of pouch 300, and previous use of pouch 300.

[0165] 50 , in step 1212 of method 1200, controller 900 determines whether pouch 300 is approved for use based on at least one factor based on information gathered from identification indicia, such as readable contrast agent identifier 312, in step 1210. Factors that controller 900 may use to determine that a pouch is not approved may include, for example, pouch 300 having reached its expiration date, pouch 300 containing a contrast agent that is not suitable for the intended injection procedure, pouch 300 containing an unauthorized substance, pouch 300 not containing enough contrast agent required for the intended injection procedure, pouch 300 having been used previously, and other factors that indicate that the contrast agent in pouch 300 cannot be safely delivered to a patient.

[0166] If the controller 900 determines that the pouch 300 is not authorized at step 1212, the controller 900 may abort the infusion procedure at step 1214 of the method. The controller 900 may issue a signal (e.g., an audio or visual message) indicating that the pouch 300 is not authorized. The controller 900 may prevent the infusion procedure from being performed until a different authorized pouch 300 is scanned and connected to the system 1000.

[0167] If controller 900 determines that pouch 300 is approved in step 1212, method 1200 may connect pouch 300 to system 1000 in step 1216. An operator may place and secure pouch 300 in agitator 600, for example, using clip 614 (see FIGS. 33A, 33B, 35B). Spike 320 of contrast tube 206 may be inserted into valve 310 of pouch 300, as shown in FIGS. 29A and 30C, either manually by the operator or automatically by controller 900 if agitator 600 includes rail 640 and carriage 650 of FIGS. 33A-33D.

[0168] 50, in step 1218 of method 1200, controller 900 reconstitutes the contrast agent in pouch 300 by actuating valves 142a, 142b, etc. and pistons 122a, 122b, etc. in the order shown in Figures 2-7, 18-22, and 39 and 40. Once the contrast agent has been reconstituted and loaded into the appropriate syringe (120a, 120b, depending on the embodiment of system 1000), an injection procedure can be initiated to deliver the reconstituted contrast agent (and any prescribed cleanser agent) to the patient through infusion set 510.

[0169] Although several examples of fluid injector systems, devices, and methods for reconstituting a solute contrast agent and injecting a reconstituted contrast agent solution are shown in the accompanying figures and described in detail above, other aspects will be apparent to and readily made by those skilled in the art without departing from the scope and spirit of the present disclosure. Accordingly, the foregoing description is intended to be illustrative rather than limiting. The invention as described above is defined by the following claims, and all modifications within the meaning and scope of the claims are intended to be embraced. [Explanation of symbols]

[0170] 110 Housing 112 Stand 114 Lid 120a First syringe 120b Second syringe 120c Third Syringe 122a First Piston 122b Second Piston 132 Stopcock drive engagement part 132a Valve seat 132b Valve seat 140 Distribution Manifold 142 Stopcock 142a First valve 142b Second valve 142c Third Valve 143 Main Unit 144 Fourth Valve 146 Fluid passage 148 fluid channels 150 Contrast Port 152 Wireless Ports 154 Filtration inlet port 156 Filtration outlet port 158 Flushing Agent Port 160 Infusion port 170 first manifold conduit 172 Second manifold conduit 200 Water for injection (WFI) tank, diluent tank 202 Main water tube 204 Branch water tube, branch water line 206 Contrast medium line, contrast medium tube 300 containers, pouches 302 Upper membrane 304 Lower membrane 306 circumferential seam 308 Orifice 310 Internal Valve 312 Identification Marks, Cleaning Agent Identifiers, Contrast Agent Identifiers 314 Film part, upper film 316 Film part, lower film 318 Internal Conduit 319 points 320 Spike 330 pouches 400 Filtration Module 402 Filtration inlet line, Filtration inlet tube 404 first filtration outlet line, first filtration outlet tube 406 Second Filtration Outlet Tube 410 filter housing 412 Inlet Port 414 Exit Port 416 Filter media 450 Pump 500 detergent tank 502 Cleaning agent tube 510 Administration lines, infusion sets 550 Liquid contrast medium tank 552 Bypass tube 600 Stirrer 602 Base 604 Bracket 610 Plate, Movable Plate, Moving Plate 612 weight 614 clips 616 Retaining pin 620 Motors, servo motors 622 Driving mechanism, driving member 624 channels 630 Counterweight 632 pins 640 Rail 650 Carriage 652 clips 900 Controller 1000 Fluid Injector Systems, Flushing / Priming Systems, Purging / Priming Systems 1100 methods RA rotation axis

Claims

1. 1. A fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, comprising: a first syringe containing a diluent; a container containing the solute contrast agent; a first valve configured to provide selective fluid communication between the container and the first syringe; a controller, delivering the diluent into the container to reconstitute the solute contrast agent into the reconstituted contrast agent solution; and delivering the reconstituted contrast agent solution into an administration line configured to be fluidly connectable to a patient; a programmed or configured controller; A fluid injector system comprising:

2. a second syringe; a second valve configured to provide selective fluid communication between a cleaning agent reservoir containing a cleaning agent, the second syringe, and one or more of an administration line; The fluid injector system of claim 1 further comprising:

3. The controller: to deliver the cleaning agent into the administration line; 10. The fluid injector system of claim 2, further programmed or configured.

4. 4. The fluid injector system of claim 3, wherein the first valve is further configured to provide selective fluid communication between one or more of a diluent tank containing a diluent, the container, the first syringe, and the administration line.

5. the fluid injector system further comprising an agitator configured to receive the container; the agitator comprising a drive mechanism configured to shake the container during reconstitution; The fluid injector system of claim 4 .

6. 6. The fluid injector system of claim 5, wherein the agitator further comprises at least one heating element configured to apply heat to the container, the solute contrast agent, and the diluent contained within the container during reconstitution.

7. 10. The fluid injector system of claim 1, wherein the container is heat treated so that the solute contrast agent reaches a temperature of at least 150°C and so that the solute contrast agent is sterilized before the agitator receives the container.

8. 8. The fluid injector system of claim 7, wherein the container is heat treated so that the solute contrast agent reaches a temperature of 200°C and is sterilized and purified by depyrogenation before the agitator receives the container.

9. a filter between the container and the first valve; the filter comprising at least one filter medium configured to filter the reconstituted contrast agent solution; The fluid injector system of claim 2 .

10. 10. The fluid injector system of claim 9, wherein the filter is positively charged to remove endotoxins from the reconstituted contrast agent solution.

11. further comprising a pump configured in fluid communication with the container, the filter, and the first syringe; the pump and the filter are disposed between a spike of the contrast line and the first valve; The fluid injector system of claim 9.

12. a second syringe; a third syringe; and a filter comprising at least one filter medium configured to filter the reconstituted contrast agent solution, wherein the first valve is further configured to provide selective fluid communication between one or more of the container, the first syringe, a diluent reservoir containing the diluent, and the filter; a second valve configured to provide selective fluid communication between one or more of the filter, the second syringe, and the administration line; a third valve configured to provide selective fluid communication between a cleaning agent reservoir containing a cleaning agent, the third syringe, and one or more of the administration lines; Furthermore, The controller: delivering the reconstituted contrast agent solution from the container to the first syringe, from the first syringe to the filter, and from the filter to the second syringe; delivering the filtered reconstituted contrast agent solution from the second syringe to the administration line; delivering the cleaning agent from the cleaning agent reservoir into the third syringe; and delivering the cleaning agent from the third syringe to the administration line; 10. The fluid injector system of claim 1, further programmed or configured.

13. The container a flexible membrane comprising a polymeric material capable of withstanding a temperature of at least 150°C and configured to expand; an inner valve configured to receive a spike in the contrast line and configured to be in fluid communication with the first valve; The fluid injector system of claim 1 , comprising:

14. 14. The fluid injector system of claim 13, wherein the internal valve is configured to passively seal the container when the spike is removed from the internal valve.

15. The controller: delivering an unused portion of the reconstituted contrast agent solution from the first syringe into the container; 15. The fluid injector system of claim 14, further programmed or configured.

16. a third syringe; and a third valve configured to provide fluid communication between the third syringe, a liquid contrast reservoir, and one or more of the administration line; The fluid injector system of claim 2 further comprising:

17. The controller: delivering a liquid contrast agent contained in the liquid contrast agent reservoir into the administration line; 17. The fluid injector system of claim 16, further programmed or configured.

18. The controller: delivering an unused portion of the reconstituted contrast agent solution from the first syringe into the third syringe; and delivering the unused portion of the reconstituted contrast agent solution from the third syringe into the liquid contrast agent reservoir; 17. The fluid injector system of claim 16, further programmed or configured.

19. further comprising at least one reader; the container comprises at least one readable solute contrast agent identifier, the detergent reservoir comprises at least one readable detergent identifier, and the diluent reservoir comprises at least one readable diluent identifier; the at least one reader configured to scan and read the at least one readable solute contrast agent identifier, the at least one readable detergent identifier, and the at least one readable diluent identifier and communicate identifier information with the controller; the controller is further programmed or configured to process the identifier information and, based on the identifier information, start and stop fluid communication between one or more of the diluent reservoir, the container, the first syringe, and the administration line, and between one or more of the cleansing agent reservoir, the second syringe, and the administration line. The fluid injector system of claim 4 .

20. 1. A flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, comprising: a first syringe; a second syringe; an administration line; a container containing the solute contrast agent, the container comprising: a flexible membrane; a polymeric material capable of withstanding temperatures of at least 150°C; and an internal valve configured to receive a spike of a contrast agent line and passively seal the container when the spike is removed from the internal valve; a first valve configured to provide selective fluid communication between one or more of a diluent reservoir containing a diluent, the container, the first syringe, and the administration line; a second valve configured to provide selective fluid communication between a cleaning agent reservoir containing a cleaning agent, the second syringe, and one or more of the administration lines; an agitator configured to receive the container, the agitator comprising: a drive mechanism configured to shake the container during reconstitution; and at least one heating element configured to apply heat to the container; controlling the first valve to deliver the diluent from the diluent reservoir into the container to reconstitute the solute contrast agent into the reconstituted contrast agent solution, deliver the reconstituted contrast agent solution into the administration line configured to be fluidly connectable to a patient, and deliver the reconstituted contrast agent solution to the patient; and a controller, controlling the second valve to deliver the irrigant from the irrigant reservoir into the administration line and deliver the irrigant to the patient; a programmed or configured controller; Equipped with Before the agitator receives the container, the container is heat treated so that the solute contrast agent reaches a temperature of at least 150°C. Flow control assembly.

21. 1. A flow control assembly for a fluid injector system for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution, comprising: a first syringe; a second syringe; a third syringe; and a filter comprising at least one filter medium; an administration line; a container containing the solute contrast agent; a first valve configured to provide selective fluid communication between one or more of the container, a diluent tank containing a diluent, the first syringe, and the filter; a second valve configured to provide selective fluid communication between one or more of the filter, the second syringe, and the administration line; a third valve configured to provide selective fluid communication between a cleaning agent reservoir containing a cleaning agent, the third syringe, and one or more of the administration lines; an agitator configured to receive the container, the agitator comprising a drive mechanism configured to shake the container during reconstitution; a controller, controlling the first valve to deliver the diluent from the diluent reservoir into the container; controlling the agitator to shake the container to reconstitute the solute contrast agent with the diluent into the reconstituted contrast agent solution; and controlling the first valve to deliver the reconstituted contrast agent solution into the filter. controlling the second valve to deliver the filtered reconstituted contrast agent solution into the second syringe and to deliver the filtered reconstituted contrast agent solution from the second syringe into the administration line; and controlling the third valve to deliver the cleaning agent from the cleaning agent reservoir into the third syringe and to deliver the cleaning agent from the third syringe into the administration line; a programmed or configured controller; Equipped with the administration line is configured to be fluidly connectable to a patient; the controller delivering the filtered reconstituted contrast agent solution and the cleaning agent through the administration line to the patient; and a flow control assembly, further programmed or configured.

22. 1. A method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system, comprising: fluidly connecting a diluent reservoir containing a diluent to a first syringe of the fluid injector system; fluidly connecting a container containing the solute contrast agent to the first syringe of the fluid injector system; delivering the diluent through the first syringe into the container to reconstitute the solute contrast agent; shaking the container to reconstitute the solute contrast agent into the reconstituted contrast agent solution; delivering the reconstituted contrast agent solution into the first syringe; delivering the reconstituted contrast agent solution from the first syringe into an administration line of the fluid injector system; A method comprising:

23. 23. The method of claim 22, further comprising sterilizing the solute contrast agent in the container by heating the solute contrast agent in the container to a temperature of at least 150°C prior to fluidly connecting the container to the first syringe.

24. 23. The method of claim 22, further comprising purifying the reconstituted contrast agent solution by passing the reconstituted contrast agent solution through a filter comprising at least one filter medium prior to delivering the reconstituted contrast agent solution into the administration line of the fluid injector system.

25. fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system; delivering the cleaning agent from the cleaning agent reservoir into the second syringe; delivering the cleaning agent from the second syringe into the administration line of the fluid injector system; 23. The method of claim 22, further comprising:

26. purging air from the fluid injector system before fluidly connecting the container containing the solute contrast agent to the first syringe of the fluid injector system; 23. The method of claim 22, further comprising:

27. fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system; priming the administration line with at least one of the diluent from the diluent reservoir and the cleaning agent from the cleaning agent reservoir before connecting the container containing the solute contrast agent to the first syringe of the fluid injector system; 27. The method of claim 26, further comprising:

28. delivering an unused portion of the reconstituted contrast agent solution from the first syringe into the container; 23. The method of claim 22, further comprising:

29. removing the container containing the unused portion of the reconstituted contrast agent solution from the fluid injector system; sending the container to a recycling facility to recover the active component of the reconstituted contrast agent solution; 30. The method of claim 28, further comprising:

30. delivering an unused portion of the reconstituted contrast agent solution from the first syringe into a liquid contrast agent reservoir; 23. The method of claim 22, further comprising:

31. using a controller of the fluid injector system to determine whether the container is approved for use in an injection procedure based on at least one factor; 23. The method of claim 22, further comprising:

32. The at least one factor is the expiration date of said container; the solute contrast agent is not suitable for injection procedures; the container contains an unapproved substance; the container does not contain a sufficient amount of the solute contrast agent required for the injection procedure; and the container has been used previously; 32. The method of claim 31 , comprising at least one of:

33. in response to the controller determining that the container is not approved for use in the injection procedure, aborting the injection procedure; 33. The method of claim 32, further comprising:

34. 1. A method for reconstituting a solute contrast agent and injecting the resulting reconstituted contrast agent solution using a fluid injector system, comprising: fluidly connecting a diluent reservoir containing a diluent to a first syringe of the fluid injector system; fluidly connecting a cleaning agent reservoir containing a cleaning agent to a second syringe of the fluid injector system; fluidly connecting a container containing the solute contrast agent to the first syringe of the fluid injector system; fluidly connecting a liquid contrast reservoir containing a liquid contrast agent to a third syringe of the fluid injector system; delivering the cleaning agent from one or more of the cleaning agent reservoirs into the second syringe; delivering the cleaning agent from the second syringe into a dispensing line of the fluid injector system; delivering the liquid contrast agent from the liquid contrast agent reservoir into the third syringe; delivering the liquid contrast agent from the third syringe into the administration line of the fluid injector system; A method comprising:

35. a container containing a solute contrast agent for reconstitution in a fluid injector system used to control operation of first and second syringes and corresponding first and second valves in a manifold for the container; The container a flexible membrane defining a cavity therein for containing the solute contrast agent, the flexible membrane comprising a polymeric material capable of withstanding temperatures of at least 150° C. and allowing the cavity to be enlarged in size; an internal valve in communication with the cavity, the internal valve configured to receive a spike associated with the fluid injector system, whereby: (I) when the spike is inserted into the inner valve, the inner valve opens, thereby, under the control of the first valve, (a) allowing a diluent to flow from the first syringe through the first valve and the inner valve into the cavity and mix with the solute contrast agent to form a reconstituted contrast agent solution in the container; (b) allowing the reconstituted contrast agent solution to flow from the cavity through the internal valve and the first valve to the first syringe, from which the fluid injector system injects the reconstituted contrast agent solution through the first valve and through an administration line into a patient; and (II) when the spike is removed from the internal valve, the internal valve closes; An internal valve; A container comprising:

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