HK1210067B - Apparatus and methods for delivery of fluid injection boluses to patients and handling harmful fluids - Google Patents

Description

Apparatus and method for delivering fluid injection pellets to a patient and for treating hazardous fluids

The present patent application is a divisional application of the invention patent application having international application number PCT/US2009/046437, international application date No. 2009/5, No. 200980131638.6, entering the chinese national phase, entitled "apparatus and method for delivering fluid injection pellets to a patient and treating hazardous fluids".

Cross Reference to Related Applications

This application claims the benefit of the following patent applications: U.S. patent application No. 61/171,240, filed 4/21 of 2009, entitled "Apparatus and Methods for delivering Fluid Injection pellets to a patient and for treating hazardous Fluids" (Apparatus and Methods for Delivery of Fluid Injection pellets to a patient and Handling of hazardous Fluids) "; U.S. patent application No. 61/153,070 filed 2/17 of 2009 entitled "Apparatus and methods for delivering Fluid Injection pellets to a patient and for treating hazardous Fluids" (Apparatus and methods for Delivery of Fluid Injection pellets to Patents and handling Harmful Fluids) "; and U.S. patent application No. 61/059,384, filed 6/2008, entitled "Apparatus and method for delivering fluid Injection pellets to Patients".

The present application is also incorporated by reference into international patent application PCT/US07/89101(WO2008/083313), filed on 12, 28, 2007 entitled "Methods and Systems for Integrated Radiopharmaceutical Generation, Preparation, transport, and Administration," entitled "Methods and Systems for Integrated Radiopharmaceutical Generation, Preparation, Transportation, and Administration," claiming the benefit of U.S. provisional patent application No. 60/910,810, filed on 4,9, 2007, "Methods and Systems for Integrated Radiopharmaceutical Generation, Preparation, and Administration," and; it also claims priority to the following two U.S. provisional patent applications, both filed on 1/2007: one is No. 60/878,334 entitled "Methods and apparatus for Handling Radiopharmaceuticals" and the other is No. 60/878,333 entitled "Pharmaceutical Dosing Methods".

Technical Field

The invention disclosed herein relates to the handling and management of pharmaceuticals, typically pharmaceuticals that are harmful or toxic in nature to humans and animal subjects, such as radioactive pharmaceuticals, commonly referred to as radiopharmaceuticals, and in particular to apparatus and methods for operating and managing radiopharmaceuticals infused into human and animal subjects, and components associated therewith. Methods and devices for handling and managing chemical agents and other fluids delivered to human and animal subjects are also included.

Background

Administration of radiopharmaceuticals or pharmaceutical agents (commonly referred to as radiopharmaceuticals) is commonly used in the medical field to provide information or images of structures and/or functions within the body, including, but not limited to, bones, vessels, organs and organ systems, and other tissues. In addition, such radiopharmaceuticals may be used as therapeutic agents to kill or prevent the growth of target cells or tissues, such as cancer cells. However, radiopharmaceuticals used in imaging and therapeutic procedures often include high radionuclides with short half-lives, which are dangerous to attending medical personnel. These agents are toxic and have a physical and/or chemical effect on attending medical personnel such as clinicians, filming technicians, nurses, and pharmacists. Excessive radiation exposure is highly detrimental to attending medical personnel due to the occupational repetitive exposure of such personnel to radiopharmaceuticals. However, due to the short half-life of typical radiopharmaceuticals and the small applied dose, the ratio of radioactive radiation risk to benefit is acceptable for individual patients. In the field of nuclear medicine, constant and repeated exposure of medical personnel to radiation from radiopharmaceuticals over an extended period of time is a serious problem.

A variety of techniques are employed in the medical field to reduce radiation exposure to attending medical personnel associated with radiopharmaceutical formation, handling, transportation, dosing, and administration of radiopharmaceuticals to patients. These techniques include one or more of the following: minimizing the exposure time of the medical personnel, maintaining a distance between the medical personnel and the radiation source, and/or shielding the medical personnel from the radiation source. Radiation shielding is of considerable importance in the field of nuclear medicine, since a certain amount of close interface between medical personnel and the radiopharmaceutical, including the patient who must or will receive the radiopharmaceutical, is unavoidable during the current practice of producing, preparing and administering the radiopharmaceutical to the patient and caring for such patient. For example, a simple patient radiation protection is disclosed in U.S. patent 3,984,695 to Colica et al. For the general handling and transport of containers of radiopharmaceuticals (bottles, vials, etc.), it is known to use shielded containers known as "pigs" and to use shielded syringes to remove the radiopharmaceuticals from the radiopharmaceutical containers and administer the radiopharmaceuticals provided to the individual patient. The radiopharmaceutical transport pig is also configured to transport the syringe. An example of shielded transport pigs is disclosed in U.S. patent 5,274,239 to Lane et al, which is incorporated by reference, and U.S. patent 6,425,174 to Reich, which is also incorporated by reference herein. An example of a shielded syringe is disclosed in U.S. patent 4,307,713 to Galkin et al, which is incorporated herein by reference. Other shielded syringes are also known from the following U.S. patents: U.S. patent 6,589,158 to Winkler; U.S. patent 7,351,227 to Lemer, and U.S. patent 6,162,198 to Coffey et al, all of which are incorporated herein by reference.

As is generally known in the field of nuclear medicine, radiation emanates in all directions from radioactive materials, and thus emanates in all directions from an unshielded container holding the radioactive material. Although the radiation may be scattered or deflected, it is generally sufficient to protect personnel from direct "shine" of the radiation unless the activity level within the container is very high. The transport pigs may be formed in various configurations to accommodate radiopharmaceutical containers (bottles, vials, syringes, etc.). One form generally includes a removable cover that allows access to the contained radiopharmaceutical container, as disclosed in U.S. patent application publication 7,537,560 to Powers et al, which is incorporated herein by reference. Such a container may be in the form of a vial with an elastomeric (e.g., rubber) stopper or septum that retains the radiopharmaceutical within the vial. When the cover of the transport pig is in place, the radiation exposure is acceptable. When the cover is opened or removed, radiation "shines" out of the opening. A common sterile delivery sequence for removing a radiopharmaceutical from a radiopharmaceutical container is to puncture an elastomeric stopper or septum with a sterile needle on a needle cannula. Typically, the exposed surface of the stopper or septum is sterilized with alcohol cotton prior to piercing the stopper or septum with the delivery needle on the needle cannula. Typically, this is also done in a clean mask and follows the procedure recommended in the pharmacopoeia <797 >.

During loading with a radiopharmaceutical, and once loaded with a radiopharmaceutical, the syringe is typically handled through a syringe shield and shielded glove box or container, but may also be transported in a suitably configured transport pig as previously described. The syringe shield is typically a hollow cylindrical structure that receives the cylindrical body of the syringe and is constructed of lead or tungsten with a lead glass window that allows the operator to view the syringe plunger and the volume of fluid within the syringe. Due to its cylindrical configuration, the syringe shield shields against emission of radioactivity in a generally radial direction along the length of the syringe body, but the two open ends of the syringe shield do not provide protection to the operator because of the radiation "shines" emanating from the two ends of the syringe shield. Devices for withdrawing a radiopharmaceutical for injection into a syringe are also known. For example, U.S. patent application publication No. 5,927,351 to Zhu et al, which is incorporated herein by reference, discloses an aspiration station for radiopharmaceutical manipulation of needle cannulae. In radiopharmaceutical delivery applications, remote control devices are also known to manage radioactive material from a needle cannula to minimize radiation exposure to the attending physician, as disclosed in U.S. patent 5,514,071 to sielfaff jr. et al or 3,718,138 to Alexandrov et al. An automated device for the controlled administration of radioactive materials is disclosed in U.S. patent 5,472,403 to Cornacchia et al, which is incorporated herein by reference. A system method of controlling an injector for injecting radioactive material into a patient is disclosed in published U.S. patent application 2008/0242915.

In addition to the difficulties introduced by the hazardous nature of radiopharmaceuticals, the short half-life of such radiopharmaceuticals complicates the administration of appropriate doses to patients. For example, in Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging procedures, the radioactivity level of a radiopharmaceutical used as a tracer is measured by medical personnel, such as a radiopharmacist or nuclear medicine technician, to determine the radioactive dose to be administered to an individual patient during a diagnostic procedure. The amount of radiopharmaceutical that is administered depends on a number of factors, including the half-life of the radiopharmaceutical, and the initial radioactivity level of the radiopharmaceutical at the time the radiopharmaceutical is injected into an individual. One known solution is to measure or calibrate the initial radioactivity of the radiopharmaceutical and to provide the injection time required for a dose (calculated from the half-life of the radiopharmaceutical) at the desired radioactivity level. Typically, the radioactivity level is determined as part of the dispensing or container filling process, as generally disclosed in U.S. patent application publication 2006/0151048 to Tochon-Ganguy et al, or measured with a separate device adapted to receive a radiopharmaceutical container, as disclosed in U.S. patent 7,151,267 to Lemer or 7,105,846 to Eguchi. The radiation detector is also placed on the syringe shield and in-line with the radiopharmaceutical delivery system. For example, U.S. patent 4,401,108 to Galkin et al discloses a syringe shield for use during aspiration, calibration, and injection of radiopharmaceuticals. The syringe shield includes a radiation detector for detecting and calibrating the radioactive dose of the radiopharmaceutical drawn into the syringe. A similar structure is disclosed in the patent to Galkin et al, but the structure in combination with a transport pig is disclosed in japanese publication JP2005-283431 assigned to Sumitomo Heavy machinery Industries. U.S. patents 4,562,829 and 4,585,009, issued to Bergner and Barker et al, respectively, and incorporated herein by reference, disclose strontium-rubidium implantation systems and dosimetry systems for use therein. The infusion system includes a strontium-rubidium radiopharmaceutical generator fluidly connected to a syringe used to supply pressurized saline. Saline pumped through the strontium-rubidium generator exits the generator and flows into the patient or waste water collector. Tubing in the line between the generator and the patient passes in front of the dosimetry probe to count the number of fissions that occur. Since the geometric efficacy (or calibration) of the probe, the flow rate through the tube, and the volume of the tube are all known, it is possible to measure the total radioactivity (e.g., millicuries) delivered to the patient. Likewise, the radioactivity measurement can be made from the blood flowing through the patient. For example, U.S. patent 4,409,966 to Lambrecht et al discloses shunting of blood flow from a patient past a radiation detector. Information on nuclear medicine imaging devices and procedures can be found in the following patents: PCT patent application publication WO 2006/051531A 2 and PCT patent application publication WO 2007/010534A 2, assigned to Spectrum Dynamics LLC, both of which are incorporated herein by reference. Portable fluid delivery units are known from us patent 6,773,673 to Layfield et al, which is incorporated herein by reference.

As noted above, examples of radiopharmaceuticals used in diagnostic imaging procedures include: positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), both techniques are non-invasive three-dimensional imaging procedures that provide information about the patient's physiological and biochemical processes. Indeed, radiopharmaceuticals are used as tracers to interact with the target region. For example, the initial step in forming a PET or SPECT image of a vessel, organ and organ system, tumor, and/or other target tissue is injecting a dose of radiopharmaceutical into a patient. The radiopharmaceutical is absorbed in certain tissues or cells within the body structure of interest and concentrates in that area. For example, Fluorodeoxyglucose (FDG) is a slight modification of the normal molecule of glucose, a basic energy fuel for cells that readily accepts radionuclides as a substitute for one of the atoms in the molecule. FDG tends to be preferentially accepted by metabolically vigorous cells, such as certain cancer cells, inflamed active muscles, or active neurons. The radiopharmaceutical "tracer" emits positrons that produce photons that are detected when the tissue is scanned at different angles and the photons pass through a detector array. The image of the three-dimensional color tracer of the selected tissue structure can be reconstructed using a computer.

With the foregoing in mind, an exemplary current practice for generating, preparing and administering radiopharmaceuticals will now be described. Typical radiopharmaceutical treatment practices in the united states include: the radiopharmaceutical is first produced by an external nuclear medicine facility at a location remote from the treatment site (typically a hospital) and then delivered to the treatment site for further preparation, e.g., for individual dosing and administration. A treatment site, such as a hospital, customizes a particular radioactive material for a particular patient to prepare for at a particular time. These substances are prepared by an external nuclear medicine facility and have sufficient radioactivity to provide the desired level of radioactivity at the target time. For example, an external nuclear medicine provider may have a specific facility equipped with a cyclotron or radioisotope generator, for example, within a lead shielded container, wherein a radiopharmaceutical, i.e., radioisotope, can be generated or formed. The refining or dose preparation step, i.e., the placement of the radioisotope in injectable form, may be performed at a site remote from the treatment site. Thus, the outside provider may provide the treatment site with a radiopharmaceutical having a desired radioactivity level at the target time. Further "personalized" dose preparation of the radiopharmaceutical may occur at the treatment site. Alternatively, the outside provider may provide a radiopharmaceutical that is ready to be injected into a particular patient "ready" at a particular time, so that the medical personnel at the treatment site need only confirm that an accurate radioactive dose is present within the radiopharmaceutical, e.g., the dose in a separate dosimetry device as previously described. In the above process, as mentioned above, the medical personnel are often in close contact with the radioactive material, so that handling and transport shielding are required to protect these personnel.

Transport pigs are commonly used to transport individual doses of radiopharmaceuticals prepared for individual patients to a treatment facility. At the treatment facility, data regarding the individual unit doses is entered into the facility computer, either manually or by reading a bar code, floppy disk or other similar data format, which may be accompanied on the transport pig or radiopharmaceutical container. When it is time to deliver a prescribed unit dose to a particular patient, medical personnel at the treatment facility must remove the syringe containing the radiopharmaceutical, for example, from a transport pig, and confirm that the dose in the syringe is within the prescribed range for the patient. Alternatively, the attending physician must deliver the radiopharmaceutical to a shielded syringe and confirm the dosage as described above. If the dose is too high, some of the radiopharmaceutical may be discarded to a shielded waste container. If the dose is too low, a different syringe may be used and/or additional medicament may be loaded into the syringe (if available). While it is possible for the attending treatment site physician to participate in the preparation of the dose, typical U.S. practice is to have the radiopharmaceutical delivered to the treatment site with the desired radioactivity level at the target time. Due to this procedure, manual handling of the radiopharmaceutical at the treatment site is limited. Nevertheless, various manual checks are required to confirm that the correct radiopharmaceutical dose is ready for injection into a particular patient. These manual verifications include visual inspection and radioactivity measurement as described above.

As with the examples described above, in PET imaging, injectable radiopharmaceuticals such as FDG (fluorodeoxyglucose) are manufactured in a cyclotron outside of a nuclear medicine facility. Thereafter, the FDG is processed into radiopharmaceutical form and transferred to individual dose containers (e.g., vials, bottles, syringes, etc.) that are loaded into transport pigs to prevent unnecessary radiation to personnel, such as radiopharmacists, technicians, and drivers responsible for the formation, handling, and transport of the FDG from the cyclotron site to the PET imaging site. Due to the short half-life of FDG, approximately 110 minutes, it is necessary to transport FDG rapidly to the [ ET imaging site. Depending on the time elapsed for transport and the initial radioactivity level of the FDG at the time of manufacture, the radioactivity level of the FDG may need to be measured again at the PET imaging site. As an example, if the radioactivity level is too high, a radiopharmacist at the PET imaging site may need to dilute the FDG with a diluent such as saline, and remove a partial volume or draw fluid to reduce the radioactivity prior to injection into the patient. Throughout this process, the operation of FDG from formation to patient injection may be entirely manual. In this process, shielding products as described above (i.e., transport pigs, syringe shields, L-blocks, etc.) are used to shield individuals from the FDG. While shielding may reduce the exposure of the radiopharmacist to radiation, the radiopharmacist may still be exposed to the radiation during manual mixing, volume reduction, and/or dilution processes required to obtain the desired dose. After injection, and often after an additional delay, the radiopharmaceutical is allowed to reach the desired area in the body and be absorbed, and the patient is usually laid on a movable bed that is slid by remote control into a circular hole (known as a gantry) for imaging scanning. Positioned around the circular hole and within the gantry are several rings of radiation detectors. In one type of radiation detector, each detector emits a brief pulse of light that impinges upon gamma rays from a radionuclide in the patient at each time. The light pulses are amplified by a photomultiplier and converted to electronic signals, which are sent to a computer controlling the apparatus and the imaging data are recorded.

For completeness, it should be noted that it is also known in the united states to deliver radiopharmaceuticals to a treatment site in a multi-dose format. As a result, the multi-dose format must be divided into individual doses for each patient at the treatment site. While the dispensing may be performed at the site of injection or administration, it is more common for radiopharmacists or nuclear medicine technicians to perform the dispensing process in a "hot room" of the treatment facility. The "hot chamber" is equipped with a cleaning hood, shielding, and a dose calibrator, all of which are expensive and durable devices. The individual radiopharmaceutical doses are then transported to a regulatory office within the treatment facility where they are administered for distribution to specific patients.

In europe, the practice of radiopharmaceutical formation and dose preparation differs from the us practice in that these activities typically occur in the "hotroom" of the treatment facility, which is typically a hospital. For example, hospitals themselves often have a cyclotron or isotope generator (such as technetium generators manufactured by Amomum pharmaceuticals Inc. (Mallinckrodt Inc. St. Louis, MO); Amoxico medicine Inc. 2636, South Clerborok, Illinois, Arlington, high, South Clinker Bruko, Illinois 6005 (Amersham Healthcare, 2636South Clearcok Drive, Arlington Heights, Illinois 60005); or general electro-medical group of Archleams Archloshimashen, Kyork, Calif., Inc. (GE Healthcare Limited, Amersham Place, Littlechallford, Buckinghamshire, United Kingdom)). Two manufacturers of shielded glove boxes are comause (cometer) in italy and remon palx (Lemer Pax) in france. Hospital personnel create or withdraw radioisotopes, perform the additional chemical steps required to create a radiopharmaceutical (radiopharmaceutical) in a timely manner, and then prepare unit doses for individual patients, typically at times close to the time at which the patient is to be injected with the radiopharmaceutical. Although an internal "hot room" has the advantage of minimizing the hazards of hazardous material transport and improving internal information transfer, the additional time and radiation burden is placed on hospital staff, as measuring the radioactivity level in different steps still depends on manually inserting the container (i.e., vial, bottle or syringe) into the dose calibrator and then adjusting the radioactivity repeatedly until the desired level is reached. Unit dose radiation levels are typically recorded manually or by a printer.

Various systems for delivering hazardous fluids are known in the art, such as disclosed in U.S. patent 6,767,319 to Reilly et al and U.S. patent application publications to Uber, III et al, which are incorporated herein by reference. Another system suitable for injecting radioactive liquids into patients is disclosed in Japanese patent publication JP 2000-350783 (see also U.S. patent application publication 2005/0085682 to Sasaki et al), assigned to Sumitomo Heavy machinery Industries. This published patent application discloses a system that dispenses a volume of radioactive fluid into a coiled tubing "medical container" located within a radioactive measurement unit. When the prescribed radioactive dose accumulates in the coiled tubing container, another syringe pushes saline through the coiled tubing container and into the patient. A similar apparatus and method is disclosed in japanese publication JP2002-306609, also assigned to Sumitomo Heavy machinery Industries. Each of the above japanese publications is incorporated herein by reference.

PCT application publication WO2004/004787 (incorporated herein by reference) assigned to the university of French Brussels-Elastemium Hospital, Inc., discloses a method by which the continuous measurement of radioactivity with a dosimeter can be eliminated. The disclosed method requires an initial calibration step, but thereafter the radioactive dose is calculated as a function of time based on the anticipated delay in radioactivity. Japanese publication JP2004-290455, assigned to kojiduo kk (nemoto Kyorindo kk), japan, discloses a radiation shielded syringe system that draws FDG from a pre-filled syringe and allows for the administration of other fluids such as saline. European patent application publication EP 1616587, assigned to the university of zurich and incorporated herein by reference, discloses a radioactive fluid dispensing apparatus that pushes FDG into a tube within a radioactive dose calibrator prior to administering saline injections of the FDG into a patient. U.S. patent application publications 2005/0203329 and 2005/0203330 to Muto et al disclose robotic automated systems that extract radioactive fluid from vials or bulk containers and inject the fluid into a plurality of unit dose syringes. The system may find application in a hospital pharmacy environment. U.S. patent application publication 2005/0277833(Williams), assigned to E-Z-EM, inc, and incorporated herein by reference, discloses an injection system for manipulating, mixing, dispensing and/or injecting a radiopharmaceutical compound. The radioactive dose is monitored by discrete detectors at several locations of the apparatus.

Disclosure of Invention

In one embodiment, a hazardous fluid transport container is disclosed that includes a housing enclosing a separate enclosure, a first fluid path element disposed within the separate enclosure and at least partially filled with a first fluid, and a second fluid path element disposed within the housing and connected to the first fluid path element. The second fluid path element is at least partially filled with a second fluid. The first fluid path element is controllably fluidly connected to the second fluid path element, and at least one of the fluid path elements is adapted to be accessed from outside the housing.

The separate closure member may be radiation shielding. At least one of the first and second fluid path members includes a coiled tube adapted to be discharged outwardly from the housing. A fluid detector may be associated with at least one of the first and second fluid path elements. The fluid detector may include at least one of a radiation detector and an air detector. The controlled fluid connection between the first and second fluid path elements may be provided by a control valve.

In another embodiment, a hazardous fluid delivery system is disclosed that includes a housing enclosing an at least partially radiation-shielding enclosure, a first fluid path disposed within the shielding enclosure and at least partially filled with a first fluid, and a second fluid path element disposed within the housing and fluidly connected to the first fluid path element. The second fluid path element may be at least partially filled with a second fluid. The pump unit is desirably in controlled fluid connection with one or both of the first and second fluid path elements for dispensing fluid from the first and second fluid path elements.

At least one of the first and second fluid path members includes a coiled tube adapted to be discharged outwardly from the housing. A fluid detector may be associated with at least one of the first and second fluid path elements. The fluid detector may include at least one of a radiation detector and an air detector.

Methods of priming a hazardous fluid delivery system are also described in detail herein. The method includes providing a fluid delivery system comprising a fluid path element, delivering a first liquid to the fluid path element, delivering a separated fluid to the fluid path element, and delivering a second liquid to the fluid path element, whereby the first liquid and the second liquid are separated by the separated fluid. The first liquid may comprise a non-hazardous liquid and the second liquid may comprise a hazardous liquid. The hazardous liquid may be a radioactive liquid. The separate fluid may be a gas such as carbon dioxide or alternatively a liquid. Solid members such as pellets may be provided in separate liquids.

In another embodiment, a method of mitigating laminar flow injection pellet dispersal is disclosed that includes injecting a first fluid into a fluid flow path through a first lumen, and injecting a second fluid into the fluid flow path through a second lumen, the second lumen being concentrically disposed about the first lumen. The first fluid may be removed from the center of laminar flow in the fluid path downstream of the first lumen through an axially centered outlet lumen. The second fluid may be removed from the fluid path that is concentric outwardly from the axially centered outlet lumen.

Further, a radiopharmaceutical fluid transport container is disclosed that includes a container body forming an interior compartment, at least a portion of which is radiation shielded, and a closure lid associated with the container body for enclosing the interior compartment. The inlet opening and the outlet opening are disposed within the container body, the closure lid, or both to allow access to the interior compartment. A syringe and a set of fluid paths connected to an outlet of the syringe may be disposed within the container. The fluid path set includes an inlet fluid path element and an outlet fluid path element. The needle cannula is disposed within the interior compartment such that at least a portion of the inlet fluid path element of the fluid path set extends through the inlet opening and at least a portion of the outlet fluid path element extends through the outlet opening. The shielded radiation window may be disposed within the closure cap. The inlet check valve may be associated with an inlet fluid path element of the fluid path set and the outlet check valve may be associated with an outlet fluid path element of the fluid path set. At least one of the inlet and outlet fluid path elements of the fluid path set may be adapted to be emitted outwardly from the container body through the inlet and outlet openings. At least one of the inlet and outlet fluid path elements of the fluid path set may be formed from a medical tubing.

Another embodiment relates to a hazardous fluid filling and transport system that includes a hazardous fluid transport container and an associated filling system. The fluid transport container includes a housing enclosing a separate enclosure, a first fluid path element disposed within the separate enclosure, and a second fluid path element disposed within the housing and fluidly connected to the first fluid path element. The inflation system is controllably fluidly connected with at least the first fluid path member and includes at least a first fluid source and a second fluid source. At least one fluid pump is associated with the first and second fluid sources to dispense fluid from the first and second fluid sources into the first fluid path element and then into the second fluid path element.

The separate closure member may be radiation shielding. At least one of the fluid path members may comprise a coiled tube adapted to be discharged outwardly from the housing. A fluid detector may be associated with at least one of the first and second fluid path elements. The fluid detector may include at least one of a radiation detector and an air detector. The controlled fluid connection between the charging system and the first fluid path element may comprise a control valve.

Further details and advantages will become apparent from a reading of the following detailed description in conjunction with the drawings in which like parts are designated by like reference numerals or symbols.

Drawings

FIG. 1 is a schematic view of a manually operated system for injecting a radioactive fluid into a patient.

Fig. 2 is a schematic cross-sectional view of an embodiment of a fluid transport container used as part of a fluid delivery system for injecting a radioactive fluid into a patient.

Fig. 3 is a schematic perspective exterior view of the fluid transport container shown in fig. 2.

Fig. 4 is a schematic view of a filling system for loading radioactive fluid into the fluid transport container of fig. 2, and which may also be used as a fluid dispensing system or platform.

Fig. 5A is a schematic view of a fluid delivery system for injecting a radioactive fluid into a patient including the fluid transport container of fig. 2.

Fig. 5B is a schematic view of a variation of the fluid delivery system of fig. 5A.

Fig. 5C is a schematic view of another embodiment of the fluid delivery system of fig. 5A.

Fig. 6A is a schematic illustration of fluid transfer of a first fluid concentrically disposed within a second fluid as applied in several embodiments described herein.

Fig. 6B is for another alternative embodiment of the multiple fluid concentric fluid transfer structure shown in fig. 6A.

Fig. 7 is an embodiment of an ideal fluid velocity profile for an injection pill provided by the devices and methods described herein.

Fig. 8A is a multi-lumen catheter that may be used to achieve a desired fluid velocity profile for multiple fluids.

FIG. 8B is an example of a fluid velocity profile for an injection pill that may be achieved with the multi-lumen catheter shown in FIG. 8A.

Fig. 9A-9I are schematic diagrams of a fluid delivery system that includes closed loop controlled fluid flow from the system to achieve a desired infusion pill profile.

Fig. 10A is a fluid delivery system adapted to inject a number of fluids into a patient in a desired injection sequence.

Fig. 10B is a graph of one possible example of a variety of fluid injection sequences provided by the system of fig. 10A.

Fig. 11 is a perspective view of an exemplary hazardous fluid collection pad suitable for absorbing spilled radioactive fluids and alerting an attending clinician.

Fig. 12 is a perspective view of an exemplary embodiment of a hazardous fluid transport container.

Fig. 13 is a perspective view showing the hazardous fluid transport container of fig. 12 in an open state.

Fig. 14 is a perspective view of an exemplary hazardous fluid syringe and associated fluid path set that may be carried by the hazardous fluid transport container of fig. 12-13.

Fig. 15A is a cross-sectional view of another embodiment of the hazardous fluid transport container shown in fig. 12-13.

Fig. 15B is a sectional view showing a modification of the hazardous fluid container shown in fig. 15A.

FIG. 16 is a schematic diagram of an embodiment of detecting radioactivity of a radioactive fluid in a fluid path set including a tube.

Fig. 17A-17C are schematic diagrams of additional embodiments of the structure for detecting radioactivity shown in fig. 16.

FIG. 18 is a cross-sectional view showing a separation structure for isolating two different fluids in the fluid paths used in the several embodiments described herein.

Detailed Description

To facilitate the description hereinafter, spatially oriented terms (if employed) shall relate to the orientation of the referenced embodiment as it is oriented in the drawings or otherwise described in the following detailed description. It should be understood, however, that the embodiments described below may assume many alternative variations and configurations. It should also be understood that the specific devices, features and components illustrated in the attached drawings and described herein are merely exemplary and should not be considered in a limiting sense.

The first cardiac contrast studies in the prior art involved rapidly manually injecting a nuclear medicine tracer or radioisotope into a tube connected to a patient's vein, and then rapidly injecting a volume of saline to flush the radioisotope from the tube and patient's vein. A series of contrast images are taken as the isotope flows through the right heart, pulmonary artery, lungs, pulmonary veins, left heart and aorta. For this study to be most useful, nuclear medicine tracers are required to be in the form of "sealed" or "compact" pills, and it is particularly desirable that there be no two peaks in the time activity profile. The volume of tracer being injected can be a fraction of milliliters (ml) up to a few milliliters. The use of a sealed pill results in a preferred first pass contrast and/or data that can be used for subsequent analysis. The sealed pill is required to be compact and avoid multiple peaks and a significantly slow ascending or descending slope. The disclosure herein is applicable to nuclear medicine with shielding and other requirements, as well as all other medical fluid delivery applications that do not require radiation shielding or radiation measurement aspects. Interference with maintaining a seal or compact pill may occur during the fluid delivery phase and within the patient himself. The disclosure herein uses the first pass through the heart contrast procedure as background for explaining the various concepts and methods of the present invention, and the various concepts and methods explained herein should not be considered limited to this one particular application. Other non-limiting example applications will also be described herein and are well known to those skilled in the medical arts. Furthermore, the manual process of injecting a nuclear tracer, turning the stopcock, and then injecting a saline flush exposes the technician to radiation from the radiopharmaceutical.

It is known that some factors can cause the infusion pill to become elongated, stained or deformed, and that such factors can include laminar or turbulent fluid flow in the fluid components, tubing transitions, elbows, roughness that can introduce turbulent or mixed flow into the injection stream, and volume or "dead volume" caused by volumetric expansion of expandable elements, such as pressurized medical tubing that can collapse when pressure is reduced. Possible solutions provided by the invention for the volume effect include: pre-pressurizing an expandable member of a fluid delivery system prior to injection of a drug fluid. For reducing fluid flow paths, transitions, bends and internal roughness, it is possible to minimize turbulence that can cause mixing flow at the beginning and end of an injection pill.

In laminar flow conditions, it is well known in the fluid art that the fluid in the center of a straight pipe moves at twice the average velocity of the fluid profile, and that the fluid velocity has a substantially parabolic curve with zero velocity at the wall surface. Thus, in the present radiopharmaceutical application, when the fluid changes from one type (or drug) to another, the new drug (second liquid) moves quickly down the center of the tube, but only slowly flushes the first fluid from the tube near the wall. For small Inner Diameter (ID) tubing typically used in medical fluid delivery applications, medical fluid delivery systems typically operate in the laminar flow range. In one aspect of the invention, it is desirable to separate the pills by a solid or gaseous "plug".

Other factors that affect an injection pill can be patient characteristics such as vein volume, venous branches that result in inadequate flushing (e.g., rapid inflow but then reduced outflow at the rate of blood flow), stretching or distension of the vein, poor venous valves, and reverse flow. As is known, there are natural variations in human body in venous volume and venous branching that vary from person to person. It is also known that veins have a branched structure so that blood can still return to the heart, regardless of the tight or relaxed state of the pill through the muscles. Table I below gives the approximate blood flow volumes for a typical vein segment of an adult.

From the above, it can be appreciated that there is a considerable volume in the vein between the standard antecubital injection site and the Superior Vena Cava (SVC). If the flush volume after injection is insufficient to push the injection pellet out into the superior vena cava, once the injection is stopped, the pellet will slow down to blood flow and move out into the superior vena cava more slowly. Thus, according to the present invention, it is desirable for the average adult to provide a flush volume of greater than 20ml, preferably 40 to 60ml, and less for children.

Venous branching worsens this volume effect and in some cases it is not possible to avoid double-peak pellets because the fluid path through one branch is longer than the fluid path of the other branch. For example, intravenous injections into the back of the hand may suffer from this effect to a greater extent because of the additional volume of the vein and the branches that appear in the forearm.

In operation, the venous behavior behaves like a canvass fire hose, which expands under pressure and collapses when the pressure disappears. If the vein is partially or fully collapsed, most of the initial injected volume will be diverted to expand the vein and forward motion will be delayed. Furthermore, veins often have a flap that ensures one-way flow towards the heart, so that when the vein is compressed by motion, the compression helps to pump blood flow back to the heart. If the venous valve is damaged, the injected fluid may flow upstream within the vein. Therefore, it is desirable to inject a substantial volume of saline in accordance with the present invention prior to injecting the drug (in the examples herein, the radioactive fluid).

If a mechanically powered injector is used as the fluid manager, inertia limits the acceleration of the mechanical parts and thus the time to fluid inject the pellets up. Furthermore, mechanical hesitation may be significant when the rearward motion becomes forward in a power injection situation, as the drive motor must move a certain amount so that the motor's force is transmitted through the mechanical gear and driven to build pressure to drive the fluid. This inertial limitation can have a negative impact on the injection pellet properties.

Features disclosed herein relate to an improved fluid injection system and associated method for time-critical contrast studies. The desired result of a fluid injection system is the ability to deliver "compact" or "compact" pellets of injection fluid to form or enhance the first pass image and corresponding data. However, in some cases, extremely "sharp" shot injections may be unnecessary or even undesirable, such as if the nuclear medicine count rate (density) limitations may mean a better temporal width for the shot, or a larger venous and right intracardiac flow or mixing effect may be sufficient to deform the injection shot such that even an infinitely compact shot injected into an arm may significantly break apart or round before reaching the desired area. An advantage of this system that can deliver extremely sharp pellets is that this capability enables a computer control system (as described herein) to controllably and repeatedly deliver less sharp pellets, or even more complex or effective to deliver any pellet shape or profile as desired by the operator or required by the medical procedure. Although the following discussion relates to the first general nuclear medicine application, the concepts herein are applicable to other applications such as, but not limited to, nuclear medicine drug perfusion quantification, delivery of hyperpolarized C-13 over a distance of 10 feet and in small volumes of a few milliliters, Computerized Tomography (CT) trial pellet injection (typically 20ml of contrast agent), magnetic resonance angiography and functional imaging (typically 10-30ml of drug), study of drug (metabolic) kinetics or pharmacodynamics, receptor pharmacokinetic studies, animal injection (typically much less than 1ml of drug), and high viscosity angiography (lubricated by a low viscosity fluid surrounding a high viscosity contrast fluid as described herein). In the case of high viscosity angiography, small "clumps" or "debris" of contrast agent can cause its movement through the vessel to be tracked and used to help measure blood flow.

Fig. 1 shows a generic prior art manual fluid delivery system comprising a needle cannula 1010, typically a 3ml needle cannula, containing a nuclear medicine tracer 1011 and connected to a stopcock 1030. Also connected to stopcock 1030 is a needle cannula 1020, typically a 20ml needle cannula, which is filled with saline 1021. Saline 1021 is used for priming (e.g., removing air) from the fluid path including connecting tube 1040 that terminates at connection 1050 to the IV catheter. After system priming, the system is connected to an IV catheter that has been previously inserted into the patient.

One challenge in delivering tight pellets is to manually actuate the needle cannula 1010, 1020 quickly and uniformly. It is rather easy to push a small amount of tracer 1011 quickly. However, stopcock valve 1030 must be turned to stop flow in tube 1040 and then flush saline delivered quickly. In a 20 or 25ml syringe 1020, the saline flush is typically 15 to 20 ml. It is difficult to build sufficient pressure using such a large needle tube 1020 to quickly deliver the pellets through, for example, a 22 gauge IV catheter. If the volume of tube 1040 is large enough to contain all of the tracer 1011 (fluid or drug) within the syringe 1010, it does not begin to enter the patient until pushed by the saline 1021 (or other fluid or drug). Thus, in this situation, the delay in rotating the stop cock 1030 does not deform the pellet because it has not yet entered the patient's arm 1060. In other cases, connecting tube 1040 is relatively short and the volume of tracer 1011 or other fluid may be 1 milliliter or more, so a time delay in rotating stopcock valve 1030 may be appropriate. In addition, in some cases, additional drugs, e.g., cardiotonic agents such as adenosine, are injected through some or all of the length of connecting tubing 1040. In this case, the tracer 1011 entering into the perfusion fluid is carried along as the other drug is perfused at its perfusion rate, causing the injected pellets to break up.

Fig. 2 illustrates an embodiment of a drug transport container 1100 that is part of the fluid injection system described in fig. 4-5 to overcome one or more obstacles to complete a tight pellet injection. The drug delivery container 1100 and the fluid injection system described in fig. 4-5 are adapted to provide a tight pellet injection for a patient to receive a drug, and the container 100 and the system may be used in the procedures exemplified herein. The drug delivery container 1100 and associated system of fig. 4-5 implement the various "protocols" previously described in connection with achieving tight pellet injection in humans and animals. The drug transport container 1100 includes a housing or closure 1110. The drug transport container 1100 includes fluid path elements 1150, 1160, and 1165 in the form of medically connected tubes. Fluid path elements 1160 and 1165 join to form fluid path element 1150. In the present invention, to explain the features of the illustrated embodiment, for exemplary purposes, the fluid path element 1160 may be referred to as a first fluid path element, while the fluid path element 1150 may be referred to as a second fluid path element, and the fluid path element 1165 may be referred to as a third fluid path element. As schematically shown, one desirable form of the fluid path elements 1150, 1160, and 1165 is a coiled tube or, optionally, any fluid conduit or volume having separate inlets and outlets such that the fluid volume is brought downstream by the fluid flow through the conduit. These fluid path elements may be physically mounted within or integral with a tray or container to allow a user to place them as a single unit within the drug delivery container 1100. Although individually designated as unique or separate fluid path elements 1150, 1160, and 1165 in the present invention, which are intended for exemplary purposes only in explaining the features of the present invention, these elements may be combined or eliminated to arrive at equivalent fluid carrying flow paths known to those skilled in the art of fluid transfer. Since the tubes comprising the various elements are in the form of coils, one or more of all of the fluid path elements 1150, 1160, and 1165 may be discharged outwardly from the housing 1110. In fig. 4-5 discussed herein, fluid path elements 1150, 1160, and 1165 in the form of coils are omitted for clarity.

The fluid path element 1160 is adapted to contain the radiopharmaceutical and is surrounded by a shield element 1120, 1121, 1122 of sufficient thickness, desirably made of tungsten, lead, or other shielding material, to protect medical personnel from radioactivity emitted by the radiopharmaceutical fluid in the fluid path element 1160. The shield 1120 is desirably in the form of an enclosure surrounding the fluid path element 1160. Fluid path connectors 1192, 1193 connect fluid path elements 1165 and 1160, respectively, to an upstream fluid source, while fluid connector 1191 connects fluid path element 1150 to a catheter inserted into the patient. Such upstream fluid sources may include, for example, a radiopharmaceutical having radioactivity and saline, the former also interchangeably referred to herein as a radiopharmaceutical. Optional valve elements 1170 and 1180 are used in the drug transport container 1100 for fluid flow control, for example, the valve elements may be one-way check valves, or may be slit silicone diaphragm valves that prevent diffusion and/or gravity-driven movement of the liquid in the fluid path elements 1150, 1160, and 1165. Optionally, valve elements 1170 and/or 1180 may be normally closed, electronically or mechanically actuated control valves, such as pinch valves or rotary valves. The sensor elements 1201, 1202 and 1203 are, for example, ultrasonic sensors or infrared sensors, which are provided to detect whether or not the fluid path elements 1150, 1165 and 1160 respectively contain liquid or gas. Optionally, the sensor elements 1201, 1202 and 1203 may include or may be solely radiation sensors for the radiopharmaceutical to measure aspects or conditions in the withdrawal or delivery of the dose. Sensor 1203, if a radioactive sensor, may be placed where it can measure the fluid from some or all of the fluid path elements 1160, as shown by sensor 1203'. Preferably attached to container housing 1110 is one or more information tags or coded storage units, such as shown by data storage device or information tag 1899, associated with one or more components of drug delivery container 1100. Fig. 3 is an external view of the exterior of the medication delivery container 1100 with a closed lid 1112 and a handle 1113 for carrying the container 1100. Desirably, a shield (not shown) is provided at the bottom of the cover 1112 and the vessel shell 1110. Thus, when the cover 1112 is closed, very little radioactivity will be ejected from the drug delivery container 1100.

Fig. 4 illustrates a priming and/or dose dispensing system 1300 adapted to interface with a drug transport container 1100 to fill the drug transport container 1100 with a radiopharmaceutical, saline, and/or other fluid. The inflation system uses many elements similar to those disclosed in U.S. patent No. 5,806,519(Evans, III et al), which is incorporated herein by reference. In this example, the bubbles, preferably CO₂(carbon dioxide) is used to isolate the required pellets of radiopharmaceutical and prevent them from mixing with the perfusion and irrigation fluids, both saline in this example. As shown in FIG. 18, CO₂The bubble 600 serves to separate two fluids 602, 604 (saline and radioactive fluids as described herein), for example, within the fluid path element 1160, because it is relatively harmless when injected in small amounts into a patient's vein. CO 2₂The gas bubbles preferably act as a fluid release agent, helping to provide maximum steepness of the pellets, but are not required according to the present invention. The fluid path elements 1150, 1160, and 1165 are preferably pre-arranged in a cassette format, preferably including features of a tray to capture any droplets, and the fluid path elements 1150, 1160, and 1165 are placed into the housing 1110 with the fluid path elements 1160 residing within the interior shield enclosure 1120. Connector elements 1192 and 1193 are connected to inflation system 1300 by mating connectors 1392 and 1393, respectively. To initiate the filling operation, the fluidThe pump 1410b pumps a volume of saline from a saline source container 1411b with associated data storage/memory element 1899a through conduit 1352 and through control valve 1342 where ports a-b are connected and through control valve 1343 where ports b-c are connected and then into fluid path element 1160. Control valve 1342 is then operated to connect ports a-c and open valve 1341 to allow flow from the CO₂CO of source conduit 1351₂May flow into the fluid path element 1160. CO 2₂The source may be a storage tank with a low pressure regulator. CO put into the pipeline₂The volume depends on the pressure and the time the control valve 1341 is open. Typically a volume of less than 1ml is delivered. Control valve 1341 is then closed and control valve 1343 is opened to connect ports a-c. From the radiopharmaceutical source container 1411a with associated data storage/memory element 1899b, the fluid pump 1410a delivers a calculated volume of a radiopharmaceutical up to a prescribed dose through the conduit 1353 into the fluid path element 1160 and pushes saline and CO in front of it₂. After the desired volume of radiopharmaceutical has been delivered into fluid path element 1160, control valve 1343 is operated to connect ports b-c and control valve 1341 is opened, less than 1ml of CO is added₂Into the fluid path element 1160. Control valve 1341 is then closed. The fluid path element 1160 is desirably sized to accommodate two COs₂The maximum volume of the pellet and the maximum volume expected of the radiopharmaceutical. Optionally, a radiation sensor 1203' may be used to measure or confirm the radiopharmaceutical dose that has been placed in the fluid path element 1160. To complete the loading of the fluid path element 1160, the control valve 1342 is operated to connect ports a-b to pump saline into the fluid path element 1160 until the first CO₂The leading edge of the "bubble" reaches a sensor 1203, which in this example is an air sensor. The initial saline in fluid path element 1160 is sufficient to have its leading edge move into fluid path element 1150. Alternatively, rather than using a sensor, the volume required to deliver the liquid rather than the gas bubble up to tube 1150 may be calculated and delivered by computer control system or control unit 1442. To complete the priming process, control valve 1342 is operated to connect ports a-c and remove saline from the vesselSource 1352 pumps saline to fill fluid path elements 1165 and 1150. The overflow can flow out of fluid connector 1191 or, optionally, can be collected by connector 1391 into a disposable waste container 1359. Alternatively, a method similar to the method of MEDRAD Stellant may be used^TMSyringe related infusion tubing (see us patent 7,018,363(Cowan et al) and us patent application publications 2004/0064041(Lazzaro) and 2005/0113754(Cowan), each of which is incorporated herein by reference). The infusion tube may remain attached to the connector 1191 to act as a cap until the operator is ready to connect the connector 1191 to the patient.

Once filled, the drug transport container 1100 is now transportable to an injection site, for example, a cardiac load cell with a first-pass video camera, such as a camera manufactured by CDL of Wexford, PA; a quiet injection chamber such as commonly used with FDG; or imaging chamber so that imaging can begin with the injection or immediately after the injection. Alternatively, the drug transport container 1100 may be non-transportable, or alternatively a transportable part of a powered injector, such as the part shown in fig. 2A-2B or fig. 18 of international application PCT/US07/89101(WO2008/083313), which has been previously incorporated by reference.

The delivery of the radiopharmaceutical from the drug delivery container 1100 may be readily understood with reference to fig. 5A-5B. It should be noted that in explaining the main subject matter in the figures, the sensor elements 1201, 1202 and 1203 in fig. 4-5 are omitted for clarity. When drug transport container 1100 is mated with a pumping unit or fluid pumping system 1400, a fluid delivery system or platform is formed, the fluid pumping system 1400 including a pump unit 1410, system control valves 1420, a saline source 1401, and other aspects (not shown), such as a computer, power supply, and user interface, which may be used for controlled, repeatable, and synchronized operation. Fluid connectors 1192 and 1193 are connected to pump outlet connectors 1432, 1433, respectively. The connector 1191 and the fluid path element 1150 of the terminal or end portion may be satisfactorily "pulled" or vented outwardly from the housing 1110 of the drug transport container 1100, the connector 1191 being for connection to an IV catheter C previously inserted into the vein of the patient P. Each fluidThe routing elements 1150, 1160, 1165 may be coiled tubing pulled or paid out from the housing 1110. Multiple obstructions may be incorporated along the fluid path elements 1150, 1160, 1165 so that the respective fluid path elements are not pulled out or emitted too far from the housing 1110. This is advantageous to ensure that any segment of the fluid path element 1160 containing the radiopharmaceutical is not pulled out of the shielded volume of the drug transport container 1100. The fluid path member 1150 is preferably of sufficient length so that it can reach and be connected to the patient's IV catheter C. In one embodiment, a small volume of fluid (a few milliliters in a few seconds) is administered as a test injection to confirm that the patient IV insertion is through. If the insertion is through, a formal injection may be given. The drug transport container 1100 may alternatively be used with the fluid pumping system 1400a of fig. 5B, where two independent syringe pumps 1410a (1), 1410a (2) drive fluid through the two fluid path elements 1160 and 1165. The two syringe pumps may be, for example, MEDRAD Stellant^TMDouble syringes or MEDRAD Spectris Solairs Ep^TMA syringe. In all of the present inventions, the syringe or pump is computer controlled and has a user interface that allows programming and control of fluid flow devices known to those skilled in the art. For use in the present invention, the "pump", "pump unit" and "pressurizing device" may be any type of pumping device known in the medical arts, such as, for example, a syringe pump, a peristaltic pump, a rotary impeller pump, a positive displacement pump, as shown in FIG. 5B, or other pumps commonly used in the medical or fluid movement arts. The control unit 1442 interacts with the data storage/memory device 1899 of the drug transport container 1100 to collect information for drug delivery and to deliver, save or record information that is subsequently useful for delivery.

As mentioned above, one of the factors that can deform the injection pellets is the expansion or extension of the vein. Also, when power injections are performed, if any compromised venous valves are present, fluid may back-flow intravenously, further delaying delivery of the drug. To reduce these variability and pellet broadening root cause factors, it is desirable to inject a volume of saline at the full rate of drug delivery to dilate and fill the vein prior to drug delivery. This can be achieved ideally by: the pump unit 1410 is connected to ports a-c of the control valve 1420 via the control valve 1420 and delivers 10 to 40ml of saline at a programmed flow rate (e.g., 4 ml/s). The control valve 1420 is then quickly operated to connect the ports a-b and re-pump saline to the patient P, preferably at the same flow rate, at which time the radiopharmaceutical is flushed from the fluid path element 1160 through the fluid path element 1150 and into the patient P. Additional saline flushes may also be delivered in sufficient quantity, for example 20 to 60ml, to flush the radiopharmaceutical from the peripheral veins into the central circulation. After the injection is complete, the above-described "cassette" or "tray" including the fluid path elements 1150, 1160, 1165 and any associated mechanical components allows these elements to be removed from the container housing 1110 as a unit and disposed of. Optionally, the fluid path elements 1160 and 1165 may be used for multiple patients, and for each patient, the terminal or end fluid path element 1150, or some sufficiently long section thereof, may be disposed of. For example, the patient end of the fluid path element 1150 may include an isolation check valve that prevents backflow, and an additional connector may be incorporated upstream of the check valve, such that the distal end of the tubing downstream of the additional connector is a short length and includes a check valve that may vary from patient to patient.

Referring to fig. 5C, which shows another embodiment of the fluid delivery system shown in fig. 5A-5B, if the fluid path element 1160 of the fluid processing container 1100 described previously is filled with drug from the end closer to the connector 1193, many effects of the shot flow dispersion can be eliminated by having the injection shot shoot out from the same end as it was filled, optionally through a short tube flowing into the patient P. This arrangement eliminates the need for the injection pellets to travel the full length of the tube. The system of fig. 5C may be used to deliver fluid from the fluid processing container 1100 in the manner described above. The drug transport container 1100 may be placed near the patient P and the connectors 1193 and 1192 may be connected to the patient by a Y-connector 1194 comprising inlet fluid connector elements 1195 and 1196 (mating with connectors 1193 and 1192, respectively) and an outlet fluid connector 1197, the connector 1197 being connected to the patient IV tubing COr a simple short tube leading to the patient IV catheter C. A longer fluid path element (e.g., tube) 1440 may be connected to the pump unit 1410 and the saline source 1401. In this embodiment, valves 1170 and 1180 are preferably electronically controlled valves that are controlled by a control unit 1442 that controls fluid pump unit 1410 in fluid pumping system 1400. Alternatively, valves 1170 and 1180 may be replaced with, for example, a computer controlled rotary valve, which may be similar to control valve 1420 described previously. For example, injecting saline through the fluid path element 1165 may prime the vein prior to injection. The valves 1170 and 1180 may then be switched such that fluid flow through the fluid path element 1160 delivers the drug, and then delivers a sufficient volume of irrigation fluid, and provides all of the advantages of the embodiments described above. One of the advantages of embodiments where the drug is loaded through a fluid connector and then delivered back through the same fluid connector is that the fluid separator can easily be a solid ball located within the fluid path element 1160 without the need to separate a gas (e.g., CO)₂). The separation ball is small enough that it can move down the fluid path element 1160. The separation ball may be constrained to remain within the fluid path element 1160 by a screen element or similar capture mechanism located within the fluid connector 1193 at the junction of the fluid path element 1160 and the fluid path element 1140, which may allow fluid to flow around the ball when the ball is blocked by the screen. Generally, in embodiments of the present invention, the drug and flush fluid are preferably separated within the fluid path element or conduit to provide a more compact pellet of injected drug. The term separation fluid includes a sufficient volume of gas, a liquid having physical properties such as an immiscibility or high viscosity that acts as a plug flow, or a solid element such as a ball as described above, sized to flow as a plug within the fluid path element as desired. Thus, in FIG. 18, CO₂The bubbles 600 may be replaced by liquid dross, or may be a solid member such as a ball that may be carried away by the fluid flow within the fluid path element.

In a variation of the fluid delivery system of fig. 5A-5C described above, if it is not desired to begin injecting or delivering saline after the saline without moving the radiopharmaceutical, the fluid path element 1165 may be eliminated. Also, for example, control valve 1420 of fig. 5A or Y-connector 1194 of fig. 5C may be incorporated into drug delivery container 1100. Furthermore, the entire pumping mechanism, including the saline source 1401 and the fluid pump unit 1410, as well as the control unit 1440, may be physically housed into one of the alternative variations.

In a variation of the fluid delivery system of fig. 5A-5C described above, if it is not desired to begin injecting or delivering saline after the saline without moving the radiopharmaceutical, the fluid path element 1165 may be eliminated. Also, for example, control valve 1420 of fig. 5A or Y-connector 1194 of fig. 5C may be physically incorporated into drug delivery container 1100. Furthermore, the entire pumping mechanism, including the saline source 1401 and fluid pump unit 1410, as well as control unit 1442, may be physically housed within one of the alternative variations.

An advantage of the system of figure 5C is that the medication is likely to be in close proximity to the patient. In the filling or dispensing system of fig. 4, the drug is filled into the ends of fluid path elements 1160 and 1165 that are furthest from fluid path element 1150. The distribution of the injection pellets can be reduced by dispensing the fluid through the fluid-filled connector elements (connectors 1192, 1191, respectively). The fluid delivery system of fig. 5C may facilitate such delivery. In international patent application PCT/US07/89101(WO2008/083313), several embodiments are disclosed in which the volume of the drug and optionally some other aspect of the injector system are mounted close to or on the arm of the patient. The present invention also contemplates that certain accompanying aspects of the medication volume and syringe system may be mounted on a vest worn by the patient, optionally including certain aspects of the ECG requirements. Alternatively, aspects of the injection system that support the volume of medication may be retained by a patient-worn object such as a pistol holster, for example, a pistol holster object on the back of the shoulder or a waist-mounted pistol holster object.

If the patient is to receive multiple injections of medication sequentially, additional fluid path elements may be added that converge at a common connection to the fluid path element 1150, or at a series of connections such that it is a common connection to the fluid path element 1150Their contents may be delivered to the patient through the fluid path element 1150. For example, certain imaging procedures use two radioisotopes, technetium and thallium. As will be apparent to those skilled in the medical arts, particularly nuclear medicine, the fluid transport container, filling and delivery system, and corresponding apparatus of fig. 2-5 may include additional elements and apparatus, optionally similar or identical to those described above, for the ability to controllably prepare and deliver multiple medicaments. In addition, many nuclear medicine procedures and many other medical procedures do not require very compact pellets in order to achieve successful results. In these cases, there is no need for CO as described above₂"bubble separation," certain specific features of the various embodiments described herein may be relaxed or removed while still maintaining certain other advantages described herein.

All of the systems, devices, and techniques provided in the present invention may be used in a variety of imaging or other medical procedures where it is useful to quickly need or first pass information or data. Cardiac first pass drugs have been described in detail. There are also other first-pass studies of nuclear medicine, for example involving the lungs and kidneys. Some PET imaging studies may use first-pass information and sometimes add longer-term information. CT angiography (CTA) is preferably a first pass study. Various isotopes and/or molecules can be used alone or in combination.

Physiologically hyperpolarized C-13 and similar atoms can be incorporated into molecules or directly used as imaging agents for Magnetic Resonance Imaging (MRI). Generally, the atoms are physiologically hyperpolarized at a distance from the imaging magnet, as is the case with the imager because the process requires a high strength magnetic field, and the two magnetic fields must not interfere with each other, as disclosed in U.S. patent 6,453,188 to Ardenkjaer-Larsen et al, which is incorporated herein by reference, (the schematic illustration of which is shown in FIG. 2). A needle containing a few milliliters of medication may be quickly moved from the polarizer to the patient, or a long tube may be used. If a long tube is used, many or all of the widening (e.g., deformation) phenomena of the injection pellets discussed herein may occur, and the strategies discussed herein may be advantageously applied. For example, rather than using coiled tubing to store the drug within the dose container, the drug is effectively transported through the fluid path element 1150 discussed previously, across a distance from the drug polarization point, and delivered to the IV catheter C of the patient P. For physiologically hyperpolarized C-13, there may also be problems associated with the material becoming polarized through contact with the wall of the carrier tube. The concentric flow arrangement described in detail herein may reduce or prevent this effect.

In CT imaging, trial pellets can be administered to measure or evaluate the response of the patient's body so that custom designed imaging pellets or larger volumes can be administered to provide optimized imaging. For example, in a CT angiography (CTA) study, the injected pellets are designed to: for a lumen to be accurately visible and viewed, the coronary arteries are of sufficient contrast but not so high as to cause calcification that obscures the lumen. In the right heart, there must be sufficient contrast to distinguish between blood and muscle, but not so high a contrast as to cause streaking or stiffening of the bundle. To determine the optimal imaging pellet profile, the pellet injection can be tested with a moderate volume of contrast agent of about 20ml or less. A series of images of the test pellets were then used to design the best imaging pellets. As discussed above, there are a number of factors that delay or deform the test pellets. If the imaging injection pellets are designed using the results of the deformation test pellets, the imaging injection pellets may provide less than optimal results. The system, apparatus and method of the present invention can be used to minimize deformation of the test pellets and also improve the sharpness of the imaging injection pellets.

In MR angiography and MRI functional imaging, injections of the order of 10, 20 or 30ml can be delivered to the patient in a single pellet. For MR angiography, the goal is to opacify the blood within the vessel. In functional imaging, the goal is to form a concentration versus time curve in various voxels of the patient. These curves can then be used to calculate perfusion to tissue. For example, in the brain, an increase in perfusion may indicate that a particular task is causing an increase in activity. The deformation pellets can distort the concentration versus time curve and make the analysis difficult, inaccurate or impossible. As discussed previously, there are a number of factors that can delay or deform the test pellets. The system, apparatus and method of the present invention can be used to minimize deformation of the test pellets and also improve the sharpness of the imaging pellets.

As described in International patent application PCT/US07/89101(WO2008/083313), mice have a blood volume of about 2ml, and thus injection of 0.2ml or more can be fatal. Injections are usually 25 to 50. mu.l (0.02ml to 0.05 ml). Tube length and Inside Diameter (ID) are typically reduced as much as possible, but tube lengths less than 12 to 18 inches are difficult. The most common small ID pipe is PE10 with an ID of 0.010 inches. The tubing had a 1.57 mul container per inch of length, so that the 18 inch tubing had a 28 mul volume, approximately equal to the injection volume. The use of intratubular gas bubbles provided by the present invention has great benefit in the case of a combined dual pathway to "pump" more perfused volume from the line when delivering the injection pellets (see figure 7 in international patent application PCT/US07/89101(WO 2008/083313)).

Embodiments of the present invention are generally directed to the delivery of fluids to animals and humans. In this case, the fluid and the elements in contact with the fluid need to be disinfected, cleaned and free of any harmful contaminants or heat sources. In medical practice in the united states, this is typically accomplished by: a disposable, pre-packaged, sterilized, disposable fluid path component is used and only once, single patient fluid source. However, this can greatly increase the cost and waste, as well as the amount of work to prepare the delivery system, and thus the chance that there may be errors in the preparation. In one set of published U.S. patents, medard corporation discloses a multi-patient delivery system that allows the use of large volume fluid containers and selected fluid path elements for multiple patients. These systems also include single patient disposables, which are discarded after each patient use because they can become contaminated by the patient, and devices or mechanisms to ensure sterilization. Examples can be found in U.S. patent No. 5,569,181, incorporated herein by reference, and other patents incorporated herein by reference. For example, the fluid path elements and fluid containers of the dispensing or filling system 1300 of fig. 4 may be periodically discarded disposables for multiple patients or uses, e.g., for disposal at the end of each day, but for subsequent patients before the fluid source is depleted or replaced. Similarly, the fluid path elements of the delivery or pumping system 1400 of fig. 5, 10 and 13 may have fluid path elements and fluid reservoirs that are preferably usable with multiple patients. Likewise, within the shipping container 1110, selected fluid path elements or element segments, e.g., 1160, 1165, and 1150, may be used for multiple patients if the most distal segment of the fluid path element 1150 is replaced, discarded, or disposed of after each patient and includes a means or mechanism to ensure sterility to prevent contamination of any multi-purpose or reusable portions. For example, in fig. 10A, a segment of fluid path element 1150, fluid path element 1152 may be removed after each patient and contain a means to ensure sterilization, such as a one-way check valve or a dual one-way check valve.

Referring now to fig. 9A-9I, in powered injector operation, a common injector servo system uses a closed loop to control the movement of a plunger within an injected syringe, as is well known in the relevant art. An exemplary power injector system 1500 is shown in fig. 9A, which includes a power injector and a fluid flow path 1502. It is desirable to obtain a tight square geometry in the injection pellet as shown in the top graph of fig. 9B. However, various factors may influence or distort the properties of the injection pellets. Such factors may include, as a reminder, physiochemical properties of the injected fluid (e.g., X-ray contrast media in the example illustrated in fig. 9B), system factors such as compliance, and patient factors. For example, the deformation phenomenon may lead to the result of injecting the pellets as shown in the bottom curve of fig. 9B. Deformed injection pellets are less desirable because the steady-state flow time is increased, the steady-state flow cannot be achieved within a short imager scan window, and with tight shot characteristics, the functional perfusion imaging operator appears to work optimally or optimally.

In view of the above, a computational method may be used to improve the control of the flow profile of an injection pellet of fluid into a patient. For example, algorithms may be used to control the operation of the pump units 1410, 1410a and to control the valves 1420 in the respective fluid delivery systems of fig. 5A-5C discussed above as examples. The algorithm is ideally based on a data-driven, per-use model of the fluid flow path 1502 shown in dashed lines in fig. 9A. To simplify each solution and improve the accuracy of the data regarding any or all of the fluid path elements within the system, a data storage device 1899, such as a bar code, memory device, or RFID, may be associated with the various fluid path elements as described in U.S. Pat. No. 5,739,508(Uber, III), which is incorporated herein by reference, which preferably includes the IV catheter C discussed above. Such data storage devices may also be associated with the housing 1110 of the drug transport container 1100 described previously, and or alternatively associated with the fluid path elements 1150, 1160, or 1165, or "cassettes" comprising such elements. Additional examples of such data storage devices are found in international patent application PCT/US07/89101(WO2008/083313) and generally relate to hazardous fluid transport containers. These devices can be used to provide a control computer that implements algorithms using the necessary information about the various fluid path elements to customize the algorithms or models for the fluid path elements present. These devices may also be used to communicate or confirm information about the contents and status of the fluid path components. Further, these devices may be used to capture and communicate information about patients and procedures, both before and after the procedure, for individual patient or hospital records, or for broader use, for example, as described in U.S. patent 7,457,804(Uber, III et al), which is incorporated herein by reference.

Fig. 9A is a generic example of such a fluid path, while fig. 5A-5C are another such example. Referring to FIG. 9C, the design may include a digital control system (e.g., a PID controller) with a flow rate limited to, for example, 0ml/s to 2 ml/s. Fig. 9C represents a closed loop control system for controlling the operation of the fluid delivery system 1500 of fig. 9A, where the controller error signal is equal to the requested flow rate minus the estimated output flow rate, and the input to the fluid flow path model is a measurement of injector motor speed.

An experimental test of the basic fluid delivery system 1500 shown in fig. 9A was performed using the test device shown in fig. 9D. Multiple attempts are made while recording the motor speed of the syringe 1501 and measurements of the distal flow rate out of the fluid flow path 1502. Set forth below is an operator 1510 (see fig. 9E) of the control or corrective action of the modeled fluid delivery system 1500, which operator is to control the modeled fluid delivery system shown in fig. 9E-9F:

the results of the attempt are compared to the results of the operation of the fluid delivery system 1500 without the control corrections provided by the foregoing operators. Fig. 9G is a schematic graph of an injection pellet generated by the fluid delivery system 1500 without control, and fig. 9H is a schematic graph of an injection pellet generated by the fluid delivery system 1500 with control provided by the operator described above. Fig. 9I is a schematic graph of the controlled and uncontrolled patterns generated by fig. 9G-9H simultaneously displayed in one graph. Comparing the graphs generated by fig. 9G-9H, it can be determined that the ascending edge of the injection pellet entering the body can be made sharp by operator-controlled operation of the fluid delivery system 1500. This controlled operation results in tighter, more square pellets, which is preferred in many cases for diagnostic and therapeutic procedures. As described herein, this ability provides the ability to more controllably and repeatedly provide the desired pellet sharpness and shape even though it is less than the maximum sharpness that can be achieved. The control model (e.g., operator) described above takes into account the volume of the fluid path elements and the actual fluid flow from the fluid flow path 1502 so that the flow out of the fluid delivery system 1500 is controlled, not just the position of the syringe plunger.

In another embodiment, different separators may be selected to separate the various fluids in order to overcome naturally occurring dispersion or mixing from laminar or turbulent flow in the fluid path elements and to some extent through transitions and dead spaces in the fluid path elements. The separator may be a gas, a solid, or to some extent a high viscosity immiscible liquid. An alternative method of overcoming the problem of laminar flow pellet dispersion is to have the drug centrally introduced into the flushing fluid as shown in fig. 6A. Drug 4000, which may be a radiopharmaceutical or any desired medicinal fluid, is pumped through drug lumen 4001 and flows down the center of the fluid path as the irrigation fluid is injected around the outside through outer lumen 4002. The irrigation fluid is delivered to the outer lumen 4002 through the inlet port 4003. Ideally, in laminar flow, there is no mixing between the layers, and as mentioned above, the central flow in the tube flows faster than the edges. Thus, with this concept, drug 4000 is provided to the center of flow faster than drug 4000 is filling the entire outer cavity 4002. More importantly, when the flow of drug 4000 ceases, the trailing edge of drug 4000 moves more quickly along its length out of outer chamber 4002. This embodiment can be used with a drug transport container 1100, the fluid path element 1160 flowing in through the drug lumen 4001, the fluid path element 1165 flowing in through the inlet port 4003, and the fluid path element 1150 being two tubes or conduits of fluid flow. In this case, it is suggested to use the drug delivery system of fig. 5B so that the drug and the saline can flow simultaneously.

Alternatively, the flush fluid may be separated from the drug 4000 when it reaches the end of the outer lumen 4002 as shown in fig. 6B. In fig. 6B, the irrigation fluid is delivered to the outer chamber 4002 through the inlet port 4003 and dispensed from the outer chamber 4002 through the outlet or exit port 4004. An outlet 4005 of the outer cavity 4002 carries the medicament 4000 out of the outer cavity 4002. If irrigation fluid is aspirated through outlet port 4004 at the same rate as it is injected into lumen 4002 through inlet port 4003, the irrigation fluid will carry medication 4000, preventing contact with the lumen wall before the irrigation fluid is aspirated at lumen outlet 4005. This is advantageous for small animal injections, where the total injection volume that can be administered to the animal is very small. At the end of the injection pellet, if the drug flow rate is reduced and the flush flow rate is increased so that the total flow remains the same, this is done at a rate such that the drug 4000 assumes a parabolic shape, as shown in fig. 7, approximating the length of the transverse lumen L, and then as it moves the length of the tube as shown in fig. 8B relative to the trailing edge of the injection pellet, the trailing portion of the injection pellet in the center will "catch up" with the main portion of the pellet. Drug 4000 will then exit in a compact, ideally rectangular curve.

Certain molecules or drugs used or in nuclear medicine or other imaging procedures have a tendency to stick or attach to various plastics. The placement of the drug within the central pellet as described herein has the benefit of: reducing the loss of drug by sticking to the walls of the tube.

Another exemplary application that may greatly benefit from embodiments in which a very viscous contrast agent, with the drug moving along the center of the tube, is delivered through a narrow catheter is angiography. Providing an appropriate amount of saline or other low viscosity fluid on the outside of a relatively viscous X-ray contrast agent may reduce the pressure drop for a given flow, thus increasing the flow for a given pressure. Another example application is vertebroplasty, in which a thick paste of bone cement is injected into the vertebral bone to repair a fracture of the bone. Additional applications include filling aneurysms, typically in the brain, or plugging desired blood vessels by selectively injecting hard or viscous materials into the blood stream, thereby embolizing certain unwanted tissues.

In the case where the pellets are smaller than the length of the tube, it is advantageous to have three concentric inlets, as shown in fig. 8A, which can independently control the flow rate of each lumen. The flushing fluid is injected through the first and third lumens 4011, 4013, and the drug 4000 is injected through the second or intermediate lumen 4012. In operation, irrigation fluid is injected through the first and third lumens 4011, 4013 and no drug 4000 is injected. The flow rate ratio within the first and third lumens 4011, 4013 is a function of the desired initial radius of the drug pellet. Then, as the flow rate of the drug 4000 injected through the drug lumen 4012 increases, the injection flow rate of the flush through the lumen 4011 decreases until the flow rate through the lumen 4011 becomes zero, forming a parabolic curve 4014 as shown in fig. 8B. As the parabolic tail curve 4014 moves along the tube or lumen L, the center 4015 catches up with the edge 4016. At the end of the injection of the pellet, the flow rate of the drug 4000 is programmably reduced while the flow rate of the flushing fluid is increased to form a parabolic tail curve 4014 for the drug 4000, as described above. These curves can be controlled such that the injection pellets occur as sharp edges at the desired location of the lumen L at the beginning and end of the injection pellet, typically at the end of the tube forming the lumen L.

Referring to fig. 10A-10B, during a first pass imaging of the heart using the fluid delivery system shown in fig. 10A, the patient's heart is loaded by treadmill or bicycle exercise, or perfused with a loading agent, such as adenosine provided from a source reservoir, for a few minutes. Fig. 10A illustrates additional features added to the previously discussed fluid delivery system of fig. 5C. In fig. 10A, the drug source 1402 comprises adenosine, which is injected by the fluid pump 1190 at a very slow rate, typically on the order of 60ml over 4 or 6 minutes, through a fluid path element 1151 connected to a patient fluid path element 1152. The injection is of saline 1401 into the patient fluid path 1152 at a flow rate of a few milliliters per second compared to the fluid contained within the fluid or drug transport container 1100, and compared to through the fluid pump system 1400 and the fluid path element 1150. There can be significant problems when a rapid saline or injected drug pellet flows into the patient fluid path element 1152. This injected bolus pushes all of the adenosine moving slowly intravenously in the patient fluid path element 1152 and patient arm from the drug source 1402 into the central circulation as a single large bolus, rather than a steady flow. This large pellet of adenosine can cause an excessive load on the patient. The system of FIG. 10A integrates control of: the heart stimulation provided by the pump unit 1190 stimulates adenosine perfusion, fluid from the drug transport container 1100, and saline from the saline source 1401 provided by the fluid pump system 1400 in an attempt to overcome this problem. As shown in fig. 10A, a programmable control unit 1442 controls the operation of the adenosine pump unit 1190, the saline and fluid injection pump unit 1410, and the control valve 1420. An exemplary sequence of flow curves (not shown to scale) that may be provided by the programmable control unit 1440 is shown in fig. 10B.

In phase 1 (as shown in fig. 10B), a slow perfusion is provided from the drug source 1402 by the pump unit 1190 through the fluid path elements 1151, 1152 of adenosine, which loads the patient's heart. When the rhythm is almost sufficient, phase 2 can begin. In phase 2, the flow of adenosine from the drug source 1402 is stopped and the flow of saline from the saline source 1401 is started. Saline from the saline source 1401 first pushes adenosine out of the patient fluid path element 1152 at the same rate as adenosine perfusion. Phase 3 begins when the saline volume is sufficient to flush most of the adenosine from the patient fluid path element 1152. The saline flow rate from the saline source 1401 is now the flow rate of the drug injection and this volume is sufficient to fill the patient's vein. Also in phase 3, the previously slow flow rate of perfusion adenosine from the drug source 1402 is maintained. The saline carries the adenosine quickly, but there are no large pellets or fragments of adenosine because the patient fluid path element 1152 has been cleaned before the saline begins its high flow rate. Once a sufficient volume of saline is provided, stage 4 can begin. In stage 4, the pump unit 1410 delivers saline from the saline source 1401 through the fluid path element 1160, rapidly propelling the radiopharmaceutical, e.g., in the drug transport container 1100, into the patient P. During phase 4, pump unit 1190 continues slow adenosine perfusion. After drug delivery, in stage 5, pump unit 1410 continues to pump saline from saline source 1401 to flush the drug out of the patient's vein. If the saline flush stops immediately after delivery of sufficient volume, there is a gap in adenosine delivery because the fluid in the fluid path element 1152 is now mostly saline. To avoid this sharp drop in delivered adenosine, the saline flow rate should be gradually decreased. Alternatively or in conjunction with this procedure, the adenosine flow rate may be increased until the patient fluid path element 1152 is mostly filled with adenosine. The saline flush may then be stopped, as shown in stage 7, with the remainder of the adenosine delivered.

Other flow profiles may be used with the systems and devices of the present invention, which are considered to be within the scope of the present invention because of the programming and operational flexibility of these systems and devices. Alternatively, a new radiopharmaceutical loading agent known as regadenoson has been formulated which does not require steady state perfusion but can be delivered as an injection pellet. The exemplary embodiment using regadenoson includes irrigating all of the fluid path elements 1150, 1160, and 1165 with saline, then delivering 5ml of standard irrigation regadenoson to the fluid path element 1165, and thereafter delivering the radiopharmaceutical to the fluid path element 1160. For the fluid dispensing or fluid delivery system 1300, additional fluid path elements or branches dispense additional regadenoson. For the fluid delivery system 1400 of fig. 5, it remains physically the same, but differs in operation. The fluid within the fluid path element 1165 is dispensed quickly followed by a sufficient volume of saline flush. The radiopharmaceutical is then dispensed from the fluid path element 1160 after a suitable delay to effect the drug, optionally preceded by additional saline, after which sufficient saline flushing occurs.

This may also be used in embodiments described herein that employ concentric flow configurations to prevent variations in the flow rate of each drug from undesirable moments of over-or under-delivery. In this case, the other drug, e.g., adenosine, may be mixed or combined with saline, which then flows over the outside of the central drug. Alternatively, if the adenosine is sufficiently diluted, it can be used as a flushing fluid on the outside of the central drug without the need to deliver saline separately.

Another feature of the present invention relates to the use of a pad or liner 200 having a disposable cloth, as shown in fig. 11, which may be used at certain locations in the fluid delivery system as shown in fig. 5A-5C, such as below or around all of the fluid connection points, to absorb or capture any radioactive "droplets" that may occur. As shown in FIG. 11, the pad or liner 200 may be an absorbent matrix fabric 202, such as the type of material used in disposable diapers. One feature of the pad or liner 200 is the association of radioactivity detectors 204, ideally distributed within a matrix web 202, the matrix web 202 being electronically connected to a dosimeter 206 as shown. A suitable dosimeter for this purpose is disclosed in U.S. Pat. No. 5,274,239 to Lane et al, which is incorporated herein by reference. In addition, a hand-held shielding wipe with an absorbent disposable cloth may be used to manipulate the pad or liner 200. The absorbable fabric forming the pad or liner 200 may also include a coloring agent so that the color changes when the fabric absorbs any liquid. In addition, it may be desirable to form the matrix web 202 as a glove with an associated micro dosimeter 206 so that it is immediately known to the attending physician if exposed to radioactive fluids. Such gloves may be wholly or partially radiation shielded in order to protect the wearer. The dosimeter may include an audible alarm that the situation has occurred, and/or provide a visual alarm, for example, to change to an intermittent flashing pattern or to change the color of the light to inform the wearer of potential radioactive emissions. Such gloves may be radiation shielding to limit exposure of the personnel concerned to radioactive radiation. Optionally, a portable gamma camera similar to that manufactured by eV Products of Saxonburg, pennsylvania may be used to scan the pad or liner 200 to locate contamination, evaluate the amount of contamination, and help determine source.

As is well known in the radiopharmaceutical industry, shielding is particularly important to protect personnel involved in the production, extraction, transportation and delivery of radioactive radiopharmaceuticals. The prior art shielding of personnel associated with handling radiopharmaceutical fluids and similar hazardous fluids has been described in the foregoing description of the invention. For example, radiopharmaceutical fluids are typically loaded and transported within a shielded syringe assembly 300, as shown in fig. 14. Shielded syringe assembly 300 includes a syringe 302 containing a radiopharmaceutical and a shield 304. The syringe 302 includes an outlet 305. Such shielded syringe assemblies 300 are well known in the art, and a typical example is shown in U.S. patent 4,968,305 to Takahashi, which is hereby incorporated by reference. As discussed above, a typical syringe volume for a radiopharmaceutical syringe may be approximately a 3ml volume, while the volume of a flushing syringe (e.g., saline) may be between 20ml and 40 ml. Certain drugs such as adenosine can also be loaded into such larger volume syringes. Neither saline flushes nor adenosine injections are radioactive, and therefore, the syringes that carry them do not require special shielding. A challenge for the radiopharmaceutical industry is to minimize exposure of personnel to radioactive radiation. For example, shipping containers (e.g., shipping pigs) are known for the shipping of syringes of radiopharmaceuticals, particularly shielded syringes. Lead lined needle transport containers, such as those available from Pinestar (Pinestar) of greenville, pa, are commonly used in medical institutions or nuclear medicine units. Typically in the form of small "lunchboxes," these shipping containers typically house a shielded needle cannula assembly 300 containing the radiopharmaceutical. Even with transport pigs or shielded transport containers, medical personnel and others often need to manipulate shielded syringes for radioactive calibration activities and other activities, such as connecting the shielded syringes to a fluid delivery system used to inject radiopharmaceuticals into patients. During these activities, personnel are exposed to radioactive emissions from the unshielded end of typical syringe shields, and in addition, during operations to fill, prime, inject, and flush the associated shielded syringe, personnel may be exposed to the presence of unshielded needles, tubing, and other fluid path components (e.g., valves, etc.).

As noted elsewhere herein, it is common practice to connect the shielded syringe assembly 300 to a stopcock valve, which is typically connected to a line leading to the patient, and a second syringe containing saline, so that a saline flush can be performed quickly after the manual injection of the radiopharmaceutical, and/or so that all or substantially all of the radiopharmaceutical can be removed from the syringe 302 and fluid path. During manual injection and rotation of the stopcock valve, the operator is exposed to ionizing radiation of the drug within the fluid path. Furthermore, manual rotation of the valve and injection causes incoherence of the injection.

In view of the foregoing background, the present invention provides an embodiment of a shielded transport container 330 as shown in fig. 12-15 that may be used to transport a shielded syringe assembly 300 and associated fluid path set 306 in a safe manner to a location where, for example, the shielded syringe unit 300 may be readily interfaced with a fluid delivery system, such as a fluid delivery system, e.g., a powered injector unit. Advantages of shielded shipping container 330 include, for example, the ability to prime fluid path set 306 to shielded syringe assembly 300 without having to remove shielded syringe assembly 300 from shielded shipping container 330. Other advantages of this system are that a tight shot injection is quickly provided to the patient, followed by a flush, while minimizing the radiation dose to the operator or technician; radiopharmaceuticals may be provided within the generally shielded syringe assembly 300 and reduce radiation exposure to the operator and nearby personnel.

To operate the system, generally, a shielded syringe assembly 300 containing a radiopharmaceutical is connected to an irrigation fluid path set 306 (which may be irrigated before or after connection to the syringe 302). The perfusion may be anywhere, for example, at the manufacturer, in a hot room, or at the site of patient injection. The fluid path set 306 is connected to a patient and syringe system 400 that can quickly deliver a sufficient volume of fluid to flush the radiopharmaceutical into the patient. The shielded transport container 330 may also be configured to be physically introduced with a syringe or "worn" by the patient. In the embodiment of FIG. 13, in an exemplary operation, an operator opens the lid of the container 330, manually injects the radiopharmaceutical from the shielded syringe assembly 300 into the fluid path set 306, and rapidly closes the lid. The exposure of the operator is limited to this brief period of time. While waiting to inject the patient, or flush the irrigation fluid path set 306, the operator does not hold the shielded syringe assembly 300. The volume of the fluid path set 306 is selected such that no radiopharmaceutical leaves the shielded transport container 330 until the saline flush within the syringe system 400 is complete. When the radiopharmaceutical is to be delivered to the patient, the injector system is triggered, which controllably pushes flush saline into and through the set of irrigation fluid paths 306, controllably flushes away the irrigation fluid previously located within the set of fluid paths 306, thereafter flushes the radiopharmaceutical, and finally flushes some of the irrigation fluid into the patient. In an alternative embodiment, one of which is shown in fig. 15B, a mechanical push rod 380 or other structure may be used so that the radioactive dose to the operator from opening the cap to move the radiopharmaceutical from the syringe 302 into the fluid path member 306 is also further reduced, if not eliminated. The pushrod 380 may be of a material sufficient to shield or include a shielding element 386 to reduce radiation exposure to the operator. The shielded transport container 330 also optionally has a fixture 381 for the push rod 380 to prevent accidental actuation of the push rod 380. This feature is shown schematically as a thumb screw in fig. 15B. Alternatively, pushrod 380 may engage shielded shipping container 330 in a threaded locking configuration such that a certain amount of rotation is required and may be moved forward to push fluid from syringe 302 before pushrod 380 is disengaged. Alternatively, pushrod 380 may be directly connected to the powered injector system for operation without manual intervention.

The use of shielded shipping container 330 provides a highly portable and removable container unit for shielded syringe assembly 300 that can also contain droplets and leaks during shipping. Shielded transport container 330 is shown in fig. 12-13 in the form of a simple box, which is done for exemplary purposes only and may be directly connected to a container such as the aforementioned medardstein^TMThe shielded shipping container 330 constructed in this manner is also within the scope of the present invention with the housing and/or support structure of the powered injector device of the injector engaged. By "bonding", the present invention includes the following cases: the shielded transport container 330 is physically introduced into the injector device; the shielded transport container 330 is supported on a support structure associated with the syringe or fluid handling components thereof, such as a conventional syringe support tree or a conventional IV pole. The syringe 400 shown is provided for exemplary purposes only and does not include the associated support structure as described above. Alternatively, as shown, the shielded transport container 330 may be placed adjacent to the injector device 400 with a line extending from the injector device 400 to the inlet connection 314 including the inlet check valve 318. Additional mounting and integration methods, designs and systems are also shown, for example, international patent publication WO2008/011401a2 (international application number PCT/US2007/073673), which is incorporated herein by reference.

As described above, the powered fluid injector may have a dedicated support post/structure, and the shielded transport container 330 may directly engage such a support post/structure. In the case of being physically integrally connected with the injector device, additional components (not shown) may be associated with the injector device that are unique to the integral nature of the entity and/or are specifically adapted for the hazardous fluid contained within shielded syringe assembly 300. For example, the injector may have sensors to identify when the shielded transport container 330 is physically introduced to the injector, communicating this information to the on-board or external control unit 1442 that controls operation of the injector. As described elsewhere herein, a dosimeter may also be provided on the syringe and engage, for example, an aperture or opening in shielded shipping container 330, such that a radioactivity reading of shielded syringe assembly 300 may be obtained and communicated, for example, to the syringe control unit (either internally or externally). In addition, the shielded transport container 330 may be marked with an identifier (e.g., a bar code, etc.), or may have other identification/data storage or memory devices 1899 (e.g., an RFID tag or memory) that can be read and/or written to by sensors on the injector and transmitted to the injector control unit so that the control unit controls operation of the injector based on this scanned or detected information. In addition, the injector 400 or the control unit 1442 may also write or record information to the identification/data storage device 1899, which may then be used to transmit information about the procedure or the dosage received by the patient. In general, it is contemplated that the shielded shipping container 330 may be adapted to custom fit to a syringe and/or its support structure, additionally or alternatively including custom fitting a fluid connection to a fluid path element associated with the syringe.

Conventional shielding materials may be used in conjunction with the shielded shipping container 330 body, including, for example, lead, tungsten loaded plastic, lead acrylate. In addition, other embodiments of shielded transport container 330 may be customized to accommodate the shape of shielded syringe assembly 300, to accommodate changes in fluid path set 306, to accommodate changes in imaging engines or patient facilities that cooperate with shielded syringe assembly 300 and fluid path set 306, and to accommodate syringes that interface with shielded syringe assembly 300 and fluid path set 306. For example, the shielded shipping container 330 may be formed to assume the shape of the shielded syringe assembly 300, whereby the shielded syringe assembly 300 may be matingly received. Accordingly, the shielded shipping container 330 may be customized to receive the shielded needle cannula assembly 300, for example, by forming the shielded shipping container 330 from an arcuate lead plate, casting lead into a desired shape, and injection molding the radiation shielding material. Alternatively, the shielded needle cannula assembly 300 may be formed to custom fit the shielded shipping container 330.

The shielded shipping container 330 generally includes a container body portion 332 that forms an interior compartment 334 and a closure lid 336 that closes the interior compartment 334. The interior compartment 334 formed by the container body portion 332 may be sized and/or include internal structure configured to receive the needle cannula assembly 300 or assemblies 300 and to match the shape of the shielded needle cannula assembly 300 or assemblies 300. In such an alternative, the "mating" internal structure may include shielding material, while the surrounding structure of the shipping container 330 forming the shield is unshielded. A dosimeter "on-board" may also be provided within shielded transport container 330 to obtain radioactivity readings within interior compartment 334, as described in the following patents: international patent application PCT/US07/89101(WO2008/083313), and U.S. Pat. No. 5,274,239 to Lane et al, previously incorporated herein by reference. Desirably, such internal radioactivity readings are communicated to an operator of the fluid delivery system comprising the powered injector 400 and the shielded transport container 330, such as by a display on the body of the shielded transport container 330, or a display associated with the injector device 400 and/or a control unit 1442 associated with the injector device 400. Such a dosimeter may provide input to the injector control unit so that the controller may identify the contents within the shielded syringe assembly 300 based on the measured radioactivity level. In addition, a shielded radiation window 338 also desirably may be disposed on the shielded transport container 330 such that medical personnel may visually inspect the contents of the shielded transport container 330, as well as the contents of any fluid coupling elements associated with, for example, the shielded needle assembly 300 and disposed within the interior compartment 334. This visual inspection capability is of importance in the bubble detection region if priming operations involving shielded syringe assembly 300 (as will be discussed herein) do not completely expel air out of shielded syringe assembly 300 and its associated fluid path components. An internal light (not shown) may be provided within the interior compartment 334 to aid in visual inspection of the shielded needle cannula assembly 300 and the fluid path components associated therewith.

Another feature of the shielded shipping container 330 is the provision of a removable and disposable internal tray unit, as shown schematically in FIG. 13 and designated by reference numeral 335, or may be a similar structure within the internal compartment 334, which may simply be discarded as hazardous medical waste after the shielded needle cannula assembly 300 has been removed once the contents of the shielded needle cannula assembly 300 have been dispensed into a patient. Removable tray or structure 335 may include an inner wall 355 or similar support element to support shielded needle cannula assembly 300 and/or to retain fluid path 306 within interior compartment 334. As mentioned in connection with fig. 11, a pad or liner 200 may be used around the fluid connection point to absorb or capture any potentially radioactive "droplets" that may occur. Such a pad or liner 200 may take the form of a "tray" and be disposed within the interior compartment 334 to absorb leaks, drips, and splatter within the interior compartment 334. Such disposable trays may be simply removed from the shielded shipping container 330 and placed into a suitable radioactive shielded medical waste bin. Further, it will be appreciated that a liquid tight seal is required between the container body portion 332 and the closure lid 336 to prevent leakage of hazardous fluids such as radiopharmaceutical fluids. In addition, the "tray" formed by the pad or liner 200 may also contain and hold (geometrically or spatially) the various fluid path components of the fluid path set 306, as well as the needle 302 and shield 304, in a mechanical manner similar to that mentioned above in connection with fig. 4.

A pair of openings 340, 342 are formed in a front edge 344 of the container closure lid 336, generally at opposite ends of the closure lid 336. Such openings 340, 342 are aligned with similar openings 346, 348 formed in a rim 350 in the container body portion 332. A handle 352 is provided on the container body portion 332 to facilitate carrying the shielded shipping container 330.

As shown in FIGS. 13-14, a shielded syringe assembly 300 generally includes a radiopharmaceutical syringe 302 and a surrounding syringe shield 304. Such components are well known in the radiopharmaceutical industry. Fluid path set 306 is connected to an outlet 305 of syringe 302 and includes a check valve T-connector 308 and inlet and outlet connectors 314, 316 associated with an inlet fluid path element 310 and an outlet fluid path element 312, respectively, connector 308 containing a check valve 320, check valve 320 being arranged to allow fluid to flow from syringe 302 into fluid path elements 310 and 312 but not back into syringe 302. The inlet fluid path element 310 may be a straight or disc-shaped inlet fluid path element, while the outlet fluid path element 312 may be similarly configured. An example of a fluid path set substantially similar to that described above is an MRI product with a check valve integrated "T" available under the trade designation SIT 96V from medard inc. Such inlet and outlet connectors 314, 316 are desirably conventional luer-type connectors, with inlet connector 314 additionally including a check valve 318, with check valve 318 allowing flow into fluid path element 310 and thus fluid path element 312, but not in the opposite direction. The check valve 318 may also be selected to have a cracking pressure high enough that fluid does not flow out under gravity, but only when driven by flushing fluid from a syringe 400 or similar pressurized device connected to the inlet check valve 318. The check valve 318 may alternatively be located on the outlet side, associated with the outlet connector 316, or anywhere along the fluid path set 306. Optionally, there is a check valve at both ends, or a plurality of check valves are arranged along the path to provide some redundancy, so that the incidence of radioactive material droplets is minimized. Check valve 320 prevents fluid from flowing into syringe 302 through T-connector 308. The T-connector 308 includes an outlet check valve 320 that allows flow from the syringe outlet 305 to the outlet fluid path element 312. Sterile end caps 322, 324 may be associated with inlet check valve 318 and outlet connectors 314, 316, respectively.

As shown in FIG. 13, once the shielded syringe assembly 300 is placed within the shielded shipping container 330, the inlet fluid path element 310 may be associated with aligned "inlet" openings 340, 346 and the outlet fluid path element 312 may be associated with aligned "outlet" openings 342, 348, whereby the inlet and outlet connectors 314, 316 may be accessed outside of the shielded shipping container 330. The outlet fluid path element 312 has two portions, namely a section 312b located inside the shielded transport container 330 and a section 312a located outside the transport container 330. Segment 312b is used to contain the radiopharmaceutical when it is ejected from the syringe 302 for delivery to the patient and subsequent flushing, similar to the fluid path element 1160 of fig. 2, with the radiopharmaceutical for subsequent delivery. The operation of segment 312a is similar to the fluid path element 1150 of fig. 2. In this embodiment, there is no fluid path element similar to fluid path element 1165, but one may be added to achieve the full functionality of the embodiments discussed above. The outlet fluid path element 312 uses a medical tube in the shape of a disc so that medical personnel can pull the tube as needed to engage the fluid path set 306 with, for example, a catheter or IV tubing indwelling in the patient. If desired, the inlet fluid path element 310 may comprise a medical tube in the form of a disk, allowing it to be extended to a remotely located syringe. The disc-shaped segment of the outlet fluid path element 312 may be initially housed entirely or primarily within the shielded shipping container 330 for cleanliness and convenience, and the user may then pull on the tubing as desired. In addition, the "outlet" openings 342, 348 may be sized and/or include elastomeric brake linings to limit how quickly the tubing that is pulled out of the outlet fluid path element 312 from the shielded shipping container 330 may be. Preferably, there is a barrier associated with the outlet fluid path element 312 such that no portion of the inner tube section 312b can be pulled out of the shielded transport container 330. Such features may also be provided or associated with the aligned "inlet" openings 340, 346.

If desired, shielded syringe assembly 300 and fluid path set 306 may be provided as an integral box or cartridge component that "plugs" into a receiving structure (not shown) within interior compartment 334 formed by container body portion 332. Such a cartridge or cartridge may be tagged with an identifier (e.g., a bar code, etc.) or have other identifying means (e.g., an RFID tag) that can be read by a sensor within the interior compartment 334 and communicated to an associated control unit, such as one associated with a powered injector, via a wired or wireless connection, whereupon injector operation may be controlled at least in part by such scanned or detected information regarding the contents of the cartridge or cartridge within the interior compartment 334. It should be appreciated that such internal sensors within the interior compartment 334 can have other actions, including determining the presence or absence of a cartridge or cartridge; identify whether a fluid path set, such as fluid path set 306, is present, or even whether valves and connectors associated with the fluid path set are properly positioned and engaged with sensors, etc. In one embodiment, the internal sensor may be an air or air bubble detector, for example associated with the aligned sets of openings 340, 346 and 342, 348, to detect the presence of air bubbles within the inlet and outlet fluid path elements 310, 312. Light bulbs may be provided within the aligned sets of openings 340, 346 and 342, 348 to assist medical personnel in detection of air or air bubbles, as well as other activities such as priming the set of fluid paths 306 with a priming fluid such as saline as described herein.

If desired, the interior compartment 334 within the container body portion 332 may be partitioned such that the syringe 302 and accompanying syringe shield 304 are disposed in an isolated area, while the components of the fluid path set 306 discussed above are disposed in an isolated area from the syringe 302 and syringe shield 304. In such a case, the closure cap 336 may be bifurcated such that separate interior spaces for the syringe 302 and syringe shield 304 and fluid path set 306 are separately accessible. Furthermore, although the above discussion generally refers to the housing of a single shielded syringe assembly 300 within a shielded shipping container 330, this should not be construed as limiting the scope of the invention to such a single application. Shielded shipping container 330 may be ideally suited for enclosing multiple shielded needle cannula assemblies 300 containing the same or different hazardous fluids, e.g., multiple isotopes such as and thallium for single patient nuclear medicine studies. The interior compartment 334 of the container body portion 332 may be configured to receive a plurality of shielded syringe assemblies 300 and include isolated interior spaces for the syringe 302/syringe shield 304 and the fluid path set 306. Accordingly, the shielded shipping container 330 may include a container body portion 332 and a closure lid 336 having multiple sets of aligned openings 340, 346 and 342, 348 to accommodate the various fluid path sets 306. Such multiple fluid path sets 306 may be parallel and connected at designated downstream connection points such as indwelling in a patient's body catheter or prior to exiting shielded transport container 330.

As noted above, it should be appreciated that the illustrated box shape of the shielded shipping container 330 shown in fig. 12-13 should not be considered limiting. Other possible configurations other than the "lunchbox" configuration shown include a clamshell configuration or a transport pig configuration, as disclosed in U.S. patent 6,425,174(Reich) assigned to Syncor International, which has been previously incorporated herein by reference. Fig. 15A shows a modification of the basic transport pig described in the aforementioned Reich patent, resulting in a "pig-type" shielded transport container 330 according to the present invention. The Reich patent discloses the basic components of a conventional transport pig and the following discussion relates to modifying the structure to obtain a pig shielded transport container 330 as shown in fig. 15A. In fig. 15A, the inner tube section 312b of the fluid path set 306 to be shielded may be disc-shaped in the interior space, typically assigned to a needle in a transport pig, modified to provide an internal labyrinth-like path for both ends of the fluid path set 306 to exit the transport pig. The disk-shaped, outer tube subsection 312a of the fluid path set 306 may be coiled around the outside of a "pig" shielded transport container 330, as shown in fig. 15A.

The pig-type shielded shipping container 330 shown in fig. 15A also modifies the basic shipping pig in the Reich patent to include openings 346 and 348 in the side walls of the lower shell 360. The lower housing 360 is adapted to engage an upper housing or closure cap 362 via a threaded connection. The radiation-shielding members 364, 366 reside within the lower and upper housings 360, 362, respectively. The lower shield member 364 also forms the openings 340, 342. As shown in fig. 15A, the inlet fluid path element 310 passes through inlet openings 340, 346, while the outlet fluid path element 312 passes through inlet openings 342, 348. In this embodiment, the shielded syringe assembly 300 does not necessarily require a separate radiation shield 304 associated with the syringe 302 because the radiation shielding is provided by the components 364, 366. The pig-type shielded shipping container 330 alone provides sufficient shielding and the syringe 302 need not be removed from the container 330.

As described above, a desirable feature of the shielded syringe assembly 300 and shielded shipping container 330 combination is the ability to prime the fluid path set 306 with a priming fluid, such as saline, for example, as is done in nuclear medicine laboratories where preparation of a dose is performed prior to associating the shielded syringe assembly 300 to, for example, a powered injection unit 400. In particular, inlet fluid path element 310 may be connected to a source of irrigation fluid, such as saline, through inlet connector 314 and check valve 318. The inlet check valve 318 prevents saline from flowing in under the force of gravity, but only directs fluid if more pressure is provided by the syringe 400 or even a manual injection, for example, through the inlet fluid path element 314 and into the T-connector 308. Saline fills outlet fluid path element 312 with priming fluid through T-connector 308 (but not into needle 302 due to outlet check valve 320). Once outlet fluid path element 312 is primed with saline, a terminal cap 324 may be disposed over outlet connector 316 to seal outlet fluid path element 312. Once the priming operation is complete, the medical personnel can carry the shielded shipping container 330 to the room where the patient is to be injected. Preferably, the syringe 302 and the fluid path set 306 are held within a shielded container 330. Alternatively, for example, if desired, an operator may remove the primed shielded syringe assembly 300 and associated fluid path 306 and mount them to the injector 400 with sufficient or appropriate shielded power. The outlet end cap 324 may be removed and the outlet connector 316 connected to a catheter or IV line connected to the patient. The outlet connector 316 is connected to the patient and the inlet connector 314 is connected to the syringe 400. The operator then manually injects all of the radiopharmaceutical from syringe 302 into tube section 312b and closes the lid on shielded transport container 330. Thereafter, when the operator triggers the power injector 400, injection of the radiopharmaceutical fluid or other hazardous fluid within the syringe 302 may begin. Because the syringe 302 with the radiopharmaceutical is retained within the shielded shipping container 330 throughout the priming operation, radioactive emissions are minimized during the priming operation. Further, after injection of the radiopharmaceutical in syringe 302, the check valve structure within fluid path set 306 allows the entire fluid path set 306 (including inlet fluid path element 310 and outlet fluid path element 312) to be flushed with saline or other fluid such that any residual radiopharmaceutical fluid within outlet fluid path element 312 is pushed into the patient. It will be apparent that the inlet fluid path member 310 may be connected to a saline flush source and a pump device, such as a peristaltic pump, that provides pressurized saline within the fluid path set 306 to flush the radiopharmaceutical fluid into the patient. Such a pump device may also be used to perform the priming operation discussed above. Alternatively, the fluid path set 306 may be transported to the patient injection room, with the fluid path segments 310 and 312 not yet primed. The inlet connector 314 may then be connected to a syringe and the fluid path segments 310 and 312 primed before the outlet connector 316 is connected to the patient. Although shielded transport container 330 is shown in fig. 12-14 as a box-shaped structure, this should not be considered limiting as shielded transport container 330 may have any desired shape, such as the transport pig structure shown in fig. 15A described previously.

Details of the connection and preparation of the shielded needle 302 to the fluid path 306 including the closed shield 304 may be used to form a bleb at one or both ends of the radiopharmaceutical pellet, which may reduce the dispersal of the pellet as the drug flows through the length of the tube, similar to the CO in the earlier described embodiments₂The use of (1). In current practice in the nuclear medicine field, a radiopharmaceutical is caused in the needle because the needle cannula is filled from a vial using a needle to pierce a rubber septum. In this embodiment, before the syringe may be connected to the fluid path set 306The needle must be removed. In this embodiment, it is preferred that the fluid in the needle should be pulled back into the needle tube, along with a fraction of a milliliter of air. This ensures that the needle is empty and provides one of the fluid separation "bubbles" associated with the above aspects. The needle is then removed and safely discarded. When a shielded syringe 302 with shield 304 or an unshielded syringe 302 is connected to fluid path set 306, small air bubbles are present within the luer connector (typically female) of T-connector 308 and within the luer connector (typically male) of syringe 302. Therefore, unless special measures are taken, when fluid is first pushed from syringe 302, a small air bubble is always injected into fluid path element 312 b. Then, when fluid is delivered from syringe 302, preferably with the syringe held upright with the luer connector on syringe 302 facing downward, small bubbles of air previously drawn into the syringe are injected into fluid path element 312 b. By this procedure, the small air pockets of air entrap the drug pellets and help maintain a sharp pellet profile as the pellets move through the various fluid path elements on their way to the patient; the procedure is analogous to CO₂The manner in which it is used in the embodiment associated with figure 4.

The various descriptions of the present invention that relate to the use of "tray" elements or the like to spatially secure tubing segments or similar fluid path elements (e.g., some or most of the fluid path set 306) and form replaceable modules or cassettes that are easy to install by a user are highly advantageous. Furthermore, the structure has advantages for use in connection with radioactive dosimeters or dose measuring elements or devices. In many devices and methods, in which radioactive materials and fluids are present, dose calibrators are often used, which typically employ a hollow cylindrical ion chamber into the center of which a container with the radioactive dose to be measured is inserted. Such an ion chamber is manufactured, for example, by the wienerster instrument b.v. (Veenstra instruments b.v.) in the netherlands. Intego manufactured by Medara Inc. (MeDRAD Inc.)^TMPET injection system, the fluid path element, i.e. the tube, is coiled on a simple tray, in this case in cylindrical form, which is placed in a hollowFor measuring the dose. A benefit of the hollow ion chamber being used as a dose calibrator is that it effectively detects the majority of the radioactivity emitted from the material located therein, this measurement being substantially independent of the exact location of the radioactive emission material within the hollow space. Thus, ion chambers work well for measuring radioactivity within a reasonable size range for syringes, vials, and coils, but this type of radioactivity detector is large and expensive.

Alternatively, in the aforementioned U.S. patents 4,562,829 and 4,585,009 (both to Bergner) and U.S. patent application publication 2005/0277833(Williams), small localized radiation detectors are used. In the Bergner patent, there are disadvantages: only a fraction of the radioactivity to be delivered can be measured at one time. In the Williams publication, measuring radioactivity in the needle tube with only a point radiation source produces errors in the readings. In international patent application PCT/US07/89101(WO2008/083313), which has been previously incorporated by reference, an embodiment is disclosed that uses several small radioactivity sensors and geometric information to measure the radioactivity in the needle tube. This particular embodiment may be used in the systems, devices and methods of the present invention.

The radiation detection system 2000 is an alternative form of dose calibrator to the hollow cylindrical ion chamber, which is shown in fig. 16. The disk-shaped tube section 2001 is held by a tray 2002 to form a module 2003 that can be placed on a simple, generally cylindrical radiation detector 2010. Radiation detectors of this general geometry are common and include, for example, Geiger tubes, ion chambers, and solid state crystal detectors. The system 2000 works well if the entire spool piece 2001 contains substantially the same concentration of radioactive fluid. Alternatively, the system 2000 works well if only the integral of the dose is measured when the drug is flowing through the entire tubing set at a constant flow rate. External shielding (not shown) may then be employed to protect personnel from radioactivity affecting other devices, and from reaching and affecting the device. However, there may be a problem in that: this may occur if the "tight" injection pellets as described earlier in this invention are shorter than the length of the coil section 2001 such that it occupies only some volume of the coil section 2001, or if the laminar flow spreads out the injection pellets such that the concentration is not uniform over the entire length of the coil section 2001, and also if the flow is not uniform, or if the measurement to be taken is slightly different from the total dose integrated over the entire transient time. In the embodiment of fig. 16, the radiation detectors have greater radiation sensitivity in some coil sections than in others, e.g., coil section 2001a has greater radiation sensitivity than coil section 2001 b. This causes non-uniformity in response to the same radiopharmaceutical dose depending on where within the disk-shaped fluid path or tubing segment 2001 it is located.

To overcome this difficulty, a radiation detection system 2000 'as shown in fig. 17A, 17B, and 17C, according to embodiments of the present invention, the tray 2002' may be shaped to hold the fluid path segments or coil segments 2001 'such that the coils are distributed along a surface that is "equally sensitive" to the radiation detectors 2010'. For simplicity, the radiation detector 2010' and the individual geometries shown in fig. 17A, 17B, and 17C are assumed to be cylindrically symmetric, but the invention is not intended to be limited to shapes having this characteristic. For each radiation detector 2010 ', the geometry of the radiation detector 2010 ' has a surface that is a function of the R and Z axes such that at any location on the surface, a small volume of radioactive fluid will give the same radioactivity measurement on the radiation detector 2010 '. In fig. 17A, the central disk-shaped element of disk segment 2001 'is moved back a little from the surface of radiation detector 2010' to achieve this effect. If the radiation detector 2010 'is a small spherical detector, the equal sensitivity surface is a sphere around the center of the radiation detector 2010', as shown in FIG. 17B. Fig. 17C shows coil section 2001 'arranged in a hat shape that can be placed on or over radiation detector 2010'. This geometry has the benefit of facilitating the installation of the tray 2003 ', facilitating the overall fluid path design of the system 2000', which can be more easily done in a planar box for ease of manufacturing, assembly, and user interface. As shown in fig. 17C, the tray may be placed within the container body 332 and the dosimeter or radiation detector 2010 'may be part of the container body 332 or may have an aperture in the container body 332 that may open to allow the dosimeter to pass through the container and measure the dose in the fluid path element 2003'. The opening may be covered with a shield when not used for measuring radioactivity and arranged to be opened and closed without exposing the operator to any radiation.

Even when the coil section 2001 'is designed to be located on the iso-sensitive surface of the radiation detector 2010', the surface geometry will always vary from radiation detector to radiation detector, and the fluid path geometry will always vary from module 2003 'to module 2003' due to manufacturing differences in the tray 2002 'or the coil section 2001'. One way to overcome this variation of having small injection pellets in the coil section 2001 'is to measure the radioactivity at two or more locations in the coil section 2001' and average the readings to find the average error. This operation can be performed by moving the injection pellet into position, stopping to start the measurement, moving to another position, stopping and measuring again, etc., until the desired number of measurements has been made. Alternatively, the operation may be implemented by: the injection pellets are moved slowly through the coil section 2001 'and a time series of measurements are taken as they flow through the coil section 2001'.

An alternative embodiment for measuring radioactivity prior to injecting the radiopharmaceutical fluid into a patient, or prior to placing the radiopharmaceutical in, for example, a hazardous fluid transport container 1100 or 330, is to measure the radioactivity emitted from a small known and defined volume or geometry of the radiopharmaceutical fluid. Once the concentration is known, the dispensed or delivered radioactive dose is proportional to the concentration multiplied by the delivered volume by measuring the dose determined by the defined volume. This is most easily illustrated with reference to the shielded shipping container 330 shown in fig. 15B. In fig. 15B, which has the basic components previously described in fig. 15A, a radiation detector or sensor 2012 is disposed behind an aperture 2020 in a radiation shield 366. Generally surrounding the radiation detector is a further shield 364' to protect the radiation detector 2012 from external radiation. The aperture 2020 is arranged to only allow radiation from the neck section of the needle 302 to impinge on the radiation detector 2012. The syringe 302 is held in a repeatable and consistent geometric position within the shielded shipping container 330, for example, by detents, clips, or similar structural elements (not shown). In operation, when shielded transport container 330 is associated with a syringe or other fluid pressurizing device for delivery, as shown in fig. 5, the output of radiation detector 2012 is communicated to a control unit 1442, which is associated with the syringe or other pressurizing device, that converts the radiation detection measurements to a radioactive concentration using a sensitivity calibrator of known design. Injector control unit 1442 then causes the desired amount of medication to be injected into fluid path set 306, for example, by controllably moving piston pusher bar 380 for subsequent delivery to the patient, or in the case of manually delivering a full volume, the recorded concentration may be indicated at the time of delivery. Control unit 1442 may also read and optionally write information from data storage/memory unit 1899 as described above. Alternatively, the radiation detector 2012 and associated mechanical components and the shield 364' may be a reusable device associated with the control unit 1442, and the shielded transport container 330 may then simply have an aperture that is shielded except when associated with the radiation detector 2012, similar to the case of the covered opening described above with reference to fig. 17C. The measurement of the radiopharmaceutical concentration is not limited to the neck of the syringe 302. It may also be performed in other fluid path elements where the geometry with respect to the probe may be fixed and consistent where the emission of radiation from nearby fluid container elements may be minimized to minimize interference. The radioactive concentration measurement allows for an accurate estimate or preliminary guess of the volume to be aspirated or delivered. The total dose can be measured and, if necessary, corrected after fluid movement.

The various embodiments set forth in this disclosure, used in combination or individually, have all the advantages of delivery of radiopharmaceuticals and all other medical fluids. For example, the pellet acutance technique of FIGS. 6 and 9 of the present invention may be used in conjunction with the disclosure in International patent application PCT/US07/89101(WO2008/083313), which has previously been incorporated herein by reference, to provide tighter pellet characteristics.

Although the embodiments of the systems, devices and methods described above may be used in combination or individually to minimize distortion of the test pellet injection and also to improve the sharpness of the imaging pellet injection, in addition, those skilled in the art may make modifications and alterations to these embodiments for safe and effective handling of hazardous fluids such as radiopharmaceutical fluids without departing from the scope and spirit of the invention. Using the various embodiments set forth in this disclosure has all the advantages of the delivery of radiopharmaceuticals and other medical fluids. Accordingly, the foregoing description is intended to be illustrative rather than restrictive. The invention as described above is defined by the appended claims, and all changes to the invention that fall within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims (22)

1. A method of operating a system for delivering a medical fluid, the system comprising: a fluid flow path; a fluid management device adapted to deliver the medical fluid through the fluid flow path; and a controller in communication with the fluid management device, the method comprising:

determining a required flow rate of the medical fluid at a distal end of the fluid flow path based at least on a required shape of an injected pill of the medical fluid at the distal end of the fluid flow path;

initiating a fluid delivery operation by delivering a medical fluid through the fluid flow path according to a fluid delivery parameter provided to the fluid management device by the controller;

receiving, at a controller, information regarding a fluid delivery operation; and

performing, by a controller, a control function to adjust the fluid delivery parameters based on the received information about fluid delivery operations to obtain the required shape of the injection pill at the distal end of the fluid flow path.

2. The method of claim 1, wherein the received information about fluid delivery operations comprises actual or estimated measurements of the flow rate at the distal end of the fluid flow path.

3. The method of claim 2, wherein the control function adjusts the fluid delivery parameter to correct for a difference between the requested flow rate of the medical fluid at the distal end and the actual or estimated measurement of the flow rate at the distal end.

4. The method of claim 1, wherein the received information about fluid delivery operations comprises an estimated measurement of the flow rate at the distal end of the fluid flow path.

5. The method of claim 4, wherein the estimated measurement of the flow rate at the distal end of the fluid flow path is determined using a model of the fluid flow path.

6. The method of claim 5, wherein the model is based on information about at least one fluid flow path element.

7. The method of claim 6, wherein the information about the at least one fluid flow path element is provided by a data storage device associated with the at least one fluid flow path element.

8. The method of claim 1, wherein the received information about fluid delivery operations comprises an actual measurement of flow rate at the distal end of the fluid flow path.

9. The method of claim 8, wherein the actual measurement of the flow rate at the distal end is determined by a flow meter configured at the distal end.

10. The method of claim 1, wherein the fluid delivery parameters for initiating the fluid delivery operation are determined using a model of the fluid flow path.

11. The method of claim 10, wherein the model is based on information about at least one fluid flow path element.

12. The method of claim 11, wherein the information about the at least one fluid flow path element is provided by a data storage device associated with the at least one fluid flow path element.

13. The method of claim 1, wherein the fluid management device is selected from the group consisting of a syringe, a pump, a valve, and a powered injector.

14. The method of claim 1, wherein the fluid management device is a powered injector.

15. The method of claim 14, wherein performing a control function comprises adjusting a motor speed of the powered injector.

16. The method of claim 1, wherein the controller is a PID controller.

17. A system for delivering a medical fluid, the system comprising:

a fluid flow path;

a fluid management device adapted to deliver the medical fluid through the fluid flow path; and

a controller in communication with the fluid management device, wherein the controller is configured to receive information regarding a fluid delivery operation and provide fluid delivery parameters to the fluid management device;

wherein the controller is programmed to perform a control function to adjust the fluid delivery parameters based at least in part on the information regarding fluid delivery operations received by the controller to obtain a desired shape of an injection pill at the distal end of the fluid flow path.

18. The system of claim 17, wherein the received information regarding fluid delivery operations comprises actual or estimated measurements of flow rate at a distal end of the fluid flow path.

19. The system of claim 18, wherein the control function adjusts the fluid delivery parameter to correct for a difference between a requested flow rate of the medical fluid at the distal end and the actual or estimated measurement of the flow rate at the distal end.

20. The system of claim 17, wherein the fluid management device is a powered injector.

21. The system of claim 17, wherein the controller is a PID controller.

22. The system of claim 18, wherein the distal end of the fluid flow path comprises a connection device to an IV catheter.