System for the Safe Preparation and Injection of Radioisotopes

Abstract

A system for the safe preparation and injection of a radioactive isotope of H2 15 O for use in positron emission tomography (PET). The invention also relates to a safety valve for controlling the flow rate of H2 15 O used in PET, the use of said safety valve, and a method for preparing and injecting H2 15 O.

Description

[0001] This application is a divisional application of the application with the filing date of January 31, 2018, application number 201680045154.X, and invention title "System for the Safe Preparation and Injection of Radioactive Isotopes". Technical Field

[0002] In a first aspect, the present invention relates to a regulating device for a system for preparing and injecting H 2 15 2 2 15 O used in positron emission tomography (PET). The present invention also relates in a second aspect to a system for preparing and injecting H 2 15 2 2 15 O, in a third aspect to a safety valve for controlling the flow rate of H Background Art

[0003] Radioactive isotopes (also known as radionuclides) have several applications in medical treatment, imaging, and research. By emitting positrons from radioactive isotopes, PET allows imaging and measurement of physiological processes in the human body.

[0004] For example 18 18 11 11 15 15 14 13 82 82 13 13 18 18 15 15

[0005] Most systems for producing radioactive water include a cyclotron that generates a target gas. The target gas of the cyclotron is transferred to a HotCell present in a qualified laboratory environment, where the target gas is converted from 2 15 16 2 16 2 15 ​O. Then the resulting H 2 15 O is typically bubbled into the saline solution in the reservoir to trap H in the solution 2 15 O. Then the H 2 15 O solution is manually transferred from the reservoir to a suction chamber or the like, and then typically a desired dose for the patient is manually inhaled into a syringe, and then the syringe is manually transported to the PET scanning room.

[0006] Since 15 O has a short half-life, it can only be used in a system that generates the radioisotope and injects it directly into the patient's body 15 O. Therefore, due to safety aspects regarding the patient directly connected to the system, it is only used to a limited extent, for example, for research purposes or under special exemption conditions 15 O.

[0007] A key aspect of safety considerations in a system that generates a radioisotope and injects it into the patient's body is the flow of compressed gas. A cyclotron is connected at one end of such a system and delivers compressed radioactive gas, which is pressurized to 10 atm or higher. The patient is typically connected at the other end of the system through a peripheral venous catheter to establish a direct connection between the patient and the compressed radioactive gas.

[0008] Standard safety features typically involve the gas passing on one side of a semi-permeable membrane and the saline passing on the other side. A sterile filter made of a material similar to the first semi-permeable membrane will be positioned closely in front of the patient. The sterile filter will create an air lock in the event of any gas passing through the first membrane, but if the gas waste tube that directs the gas away is blocked, the pressure may rise to a higher pressure than the membrane can handle, which may allow the gas to pass through the filter and enter the patient's body. The result may be that radioactive gas is infused into the patient's body at rates ranging from hundreds of ml / min up to 1 to 2 l / min, which may lead to fatal venous air embolism.

[0009] In known valves used in such systems, the valve can be configured to have a discharge opening, where in order to release excess fluid from the system, the valve must be turned to the following configuration: a flow path is established between the inflowing fluid and the discharge opening through the valve. This requires manually or automatically turning the valve to the said configuration, and thus if a failure occurs in the system, the valve will not act as a safety valve.

[0010] Furthermore, a fundamental problem faced by the system operating with compressed gas is the need for fail-safe features to ensure that the compressed gas cannot enter other parts of the system and thereby potentially affect or damage them.

[0011] To minimize the risk level to the patient, a medical staff member manually transfers the radioactive isotope from a reservoir to the patient via a syringe. In this way, the patient is not directly or indirectly connected to the cyclotron, thereby reducing the risk of accidental infusion of radioactive gas.

[0012] Manual manipulation of the radioactive isotope is safe for the patient, but due to repeated radioactive exposure to the medical staff, it is not feasible for routine patient examinations because the medical staff is exposed to unwanted and dangerous radiation each time they perform aspiration and injection.

[0013] Typically, under this manual scenario, twice the desired radioactivity is measured in a dose calibrator and aspirated. A timer is started, and when the radioactivity has decayed due to the decay of the relevant radioactive isotope and reached the desired level, the aspirated amount is transferred to the patient. Due to the short half-life of the radioactive isotope, the timing of aspiration and injection must be very precise to determine the actual amount of radioactivity transferred to the patient.

[0014] Accordingly, there is a need for a system that can generate and inject a specific amount of H 2 15 O with high precision and at a negligible risk to both the patient and the medical staff. Summary of the Invention

[0015] In this context, an object of the present invention is to provide a regulating device, a system, a safety valve, and a method with enhanced safety features for preparing H 2 15 O and injecting it into a saline solution.

[0016] For a third aspect of the present invention, this object is achieved by providing a method for controlling H used in positron emission tomography 2 15A safety valve for achieving a flow rate of O, the valve comprising: a valve element having a flow channel extending therethrough; a valve housing having at least three valve openings, each valve opening allowing fluid to flow into or out of the valve; and at least two overflow recesses, each overflow recess having at least one outlet opening, wherein the valve element and the valve housing can be connected to form an assembled valve, the valve element and the valve housing being in contact with each other in a contact area, wherein the assembled valve can be arranged in at least two different open configurations, one of the open configurations defining a flow path through the flow channel and a set of the valve openings, and the other of the open configurations defining a flow path through the flow channel and another different set of the valve openings, and wherein in each of the at least two open configurations: each overflow recess is arranged between the valve element and the valve housing; at least two of the valve openings are connected to each other through the flow channel; at least one of the valve openings is not connected to the flow channel; the contact area forms a fluid block for preventing fluid from flowing into the at least one valve opening not connected to the flow channel; the overflow recesses are not in fluid communication with the flow channel; each overflow recess is positioned to create an interruption in the contact area, such that the overflow recesses create a safe release opening for discharging overflow fluid, and in the case of overpressure, the overflow fluid passes through the corresponding outlet opening through the fluid block, so that in the at least two open configurations, the overflow fluid is prevented from entering the at least one valve opening not connected to the flow channel.

[0017] By providing a valve including the at least two overflow recesses, when the assembled valve is arranged in the at least two different open configurations, since the fluid will pass through the overflow recesses and be discharged away from the valve, the overflow recesses ensure that no fluid will travel from the at least two valve openings connected by the flow channel to the at least one valve opening not connected to the flow channel.

[0018] The assembled valve can be arranged in a closed configuration, in which the flow channel is not connected to any of the valve openings, so that no flow path through the flow channel and the valve openings is established. In this closed configuration, the fluid present in the valve openings may also be overpressurized. If the fluid passes through the fluid block, the overflow recesses discharge the overflow fluid through the corresponding outlet openings.

[0019] Since the pressure in the overflow recesses is less than the pressure integrity of the adjacent valve openings, the pressure difference ensures that the overflow fluid will be discharged from the valve.

[0020] Thus, when an undesired pressurized fluid is not expected to enter, the valve acts as a safety valve to prevent the undesired pressurized fluid from entering one or more valve openings.

[0021] In the context of the present application, it should be understood that the pressurized fluid can also be a fluid at atmospheric pressure (about 1.01325 bar). When the system operates under normal conditions, preferably the fluid is at approximately 1 to 3 bar, preferably 1.5 to 2.5 bar, more preferably approximately 2 bar.

[0022] It should also be understood that an "undesired" fluid refers to, but is not limited to, two types of fluids: a fluid that is not expected to flow from one opening of the valve to another when the valve is in the closed configuration, regardless of the pressure of the fluid; and a fluid that has been pressurized to an undesired pressure higher than expected, for example, due to a system failure before the valve. Conversely, the term "desired" fluid refers to a fluid that is expected to pass through the valve in the open configuration under normal operating conditions.

[0023] Under such normal operating conditions of the system, and when the valve is arranged in the open configuration where the flow channels are connected to the valve openings, the amount of fluid passing through the valve is in the range of approximately 500 ml / min to 1000 ml / min.

[0024] When the desired fluid passes through the flow channel and these valve openings, the fluid may be near atmospheric pressure. When the fluid normally passes through the flow channel and these valve openings, there is no significant pressure drop.

[0025] When the valve is arranged in a system for preparing H 2 15 O and injecting it into a saline solution, the valve will act as a safety valve and will thus prevent undesired pressurized fluid from reaching a patient fluidly connected to the system and causing harm to the patient.

[0026] The safety valve will ensure that in the event of a failure in the function of the system before the valve (such as a failure that causes undesired high-pressure fluid to reach the opening of the valve and the flow channel of the valve is not connected to any valve opening), the fluid will be discharged from the valve through these overflow recesses and will not enter other valve openings.

[0027] This also applies to the case where the valve is in the open position and the patient is connected to the connecting element of the valve, where the valve opening of the connecting element is not in fluid connection with the flow path. Here, the fluid will flow between these valve openings and the flow path, and if a failure occurs and undesired pressurized fluid enters these valve openings and the flow path, the overflow fluid that enters the contact area between the valve element and the valve housing will be discharged through the recesses, which are located between the valve opening of the connecting element connected to the patient and the valve opening connected to the flow path.

[0028] Thus, regardless of the valve configuration, these depressions will act as a safety measure and do not require switching between multiple configurations, thereby enhancing the safety of the patient connected to the system.

[0029] Thus, in an embodiment, the assembled valve can be arranged in a third distinct closed configuration in which the flow channel is not connected to any of the valve openings, thereby establishing no flow path through the flow channel and the valve openings.

[0030] The contact area between the valve element and the valve housing should be understood as the area where the surface of the valve element is directly adjacent to the surface of the valve housing. The fluid block in this contact area ensures the functional tightness between the valve housing and the valve element.

[0031] In the context of the present application, the term "connected" can also be understood as fluidly connected and / or in fluid communication.

[0032] In the context of the present application, the term "fluid" includes both gases and liquids.

[0033] The at least three valve openings can have any shape that permits fluid to flow from one side of the opening to the other. These valve openings are preferably circular.

[0034] The valve housing and / or the valve element can be of any desired shape, such as cylindrical, circular, rectangular, or spherical.

[0035] The size of the valve element can vary according to the size of the valve housing.

[0036] The safety valve can be formed from materials selected from the group consisting of: inert materials, polymeric materials, metals and metal alloys, and ceramics; or made from a combination of these materials. In principle, any material that is compatible with the fluid, has sufficient strength and material properties to provide a tight fluid barrier, and can withstand sterilization can be used.

[0037] Depending on the material of the safety valve, the valve can be produced by a variety of methods, such as injection molding, turning, milling, casting, and / or 3D printing.

[0038] The valve element and the valve housing can be made of different material compositions. By constructing the valve element and the valve housing with different material compositions, a tighter fit can be obtained. The valve element can be formed from a material with a lower material strength than that of the valve housing to achieve selective rupture of the valve element rather than the valve housing during an accidental pressure increase.

[0039] In an embodiment, the valve housing further includes a connection element having a first end, a second end, and an internal fluid space, the connection element being connected to the valve housing at the second end such that the fluid space is in fluid communication with one of the at least three valve openings.

[0040] By providing the connection element, it is easy to directly connect the safety valve to different medical systems, in which valves are used to prevent pressurized fluid from entering, for example, a patient's vein or artery, and thus it is desirable to enhance the safety of the system to ensure that no overflow fluid will travel to an undesired valve opening. Such medical systems can be systems for preparing and injecting H 2 15 O, where the safety valve will ensure that the overflow fluid will not be transferred to the patient line and avoid the potential life-threatening situation of accidental infusion of fluid into the patient's circulatory system.

[0041] In an embodiment, the connection element is cylindrical. The at least three connection elements may extend radially from the housing. The at least three connection elements may have substantially equal lengths.

[0042] In an embodiment, the valve housing includes three connection elements.

[0043] In an embodiment, the at least two overflow recesses are arranged in the valve housing.

[0044] In an embodiment, the at least two overflow recesses are arranged in the valve element.

[0045] These overflow recesses can have any shape, such as curved or twisted. These overflow recesses are preferably linear.

[0046] By providing the at least two overflow recesses in the valve housing and / or the valve element, a valve that is easy to assemble with a minimum number of components is provided, making the valve cost-effective and easy to manufacture and assemble.

[0047] In an embodiment, the valve element further includes a first end and a second end defining a first longitudinal axis, and the valve housing further includes: an outer shell, the outer shell including a first end and a second end and a second longitudinal axis extending between the first end and the second end, the second longitudinal axis being coaxial with the first longitudinal axis; an internal spacing for receiving the valve element, the internal spacing being enclosed by the outer shell; and at least three valve openings arranged in the outer shell, each opening allowing fluid to flow into or out of the internal spacing, wherein at least two overflow recesses extend axially between the first end and the second end of the outer shell, wherein the valve element is axially movable along the second longitudinal axis such that a portion of the valve element can be inserted into the internal spacing of the valve housing to form an assembled configuration, and the valve element is rotatable within the internal spacing about the second longitudinal axis such that the valve element and the valve housing can be changed between at least two different open configurations, wherein when the valve element is arranged inside the internal spacing and in the two different open configurations, each overflow recess is arranged between the valve element and the outer shell.

[0048] By providing a valve element that can be inserted into the valve housing for the safety valve, the valve element can be fixed inside the valve housing, thereby preventing the valve element from moving radially relative to the first longitudinal direction, thereby establishing a very high functional tightness in the contact area and thus establishing a better fluid barrier to prevent any excessive fluid from passing through the contact area.

[0049] When a portion of the valve element is inserted into the internal spacing, the valve housing can be rotatable about the first longitudinal axis 124 of the valve element and around the valve element.

[0050] The rotation of the valve element and / or the valve housing can be automatic and / or manual.

[0051] In an embodiment, the valve housing includes three valve openings.

[0052] In an embodiment, the safety valve includes three overflow recesses.

[0053] In an embodiment, the valve element includes a flow channel.

[0054] In an embodiment, the number of these valve openings is equal to the number of overflow recesses.

[0055] In some embodiments, the valve housing includes six valve openings and / or six overflow recesses. The six valve openings and / or the six overflow recesses are preferably evenly distributed along the circumference of the valve housing and / or the valve element.

[0056] In an embodiment, the at least three valve openings are equidistantly distributed in the housing. Each of these valve openings is preferably at an angle of 120 degrees relative to an adjacent valve opening.

[0057] In an embodiment, the flow channel includes a first flow channel and a second flow channel, wherein the first flow channel and the second flow channel extend at an angle relative to each other. The angle is preferably 120 degrees.

[0058] By setting these valve openings at a substantially equal angle to the first flow channel and the second flow channel, when the valve element is arranged inside the internal spacing, the first flow channel and the second flow channel passing through the valve element will coincide with two of the at least three valve openings of the valve housing, such that two of the at least three valve openings can be connected by the flow channel.

[0059] In an embodiment, the at least two overflow recesses are arranged in the housing.

[0060] In an embodiment, the at least two overflow recesses extend between a first end and a second end of the housing and open into the first end and the second end.

[0061] In an embodiment, the at least two overflow recesses extend between and / or into the first end and / or the second end of the housing.

[0062] These overflow recesses can extend radially in the housing and have a depth up to the thickness of the housing.

[0063] In an embodiment, the at least two overflow recesses are arranged in the valve element.

[0064] In an embodiment, the at least two overflow recesses extend between and / or into the first end and / or the second end of the valve element.

[0065] By providing overflow recesses that extend the entire length of the housing or the valve element, these overflow recesses ensure that any fluid traveling along the fluid block between the valve element and the valve housing will be discharged from the valve through these overflow recesses.

[0066] In an embodiment, the connecting element extends into the internal spacing.

[0067] In some embodiments, these overflow recesses can include a material having different material properties from the housing material. This is advantageous when using the valve in a system that is subject to high pressures and / or is composed of high-strength materials such as metals or metal alloys or ceramics.

[0068] In an embodiment, the housing is cylindrical.

[0069] In an embodiment, the valve element is cylindrical.

[0070] By providing a cylindrical housing and / or valve element, a good balance is ensured between the amount of material used and the strength and stiffness of the entire valve.

[0071] In an embodiment, the flow channel and the at least three valve openings are arranged in and extend along the same plane in at least two configurations of the assembled valve.

[0072] Therefore, not much space is required to arrange the safety valve, since the inlet and outlet are both arranged in the same plane, rather than having the inlet perpendicular to the flow channel / valve openings.

[0073] In an embodiment, when the valve is in the assembled configuration, the plane is substantially perpendicular to the first axis and the second axis.

[0074] It should be understood that a plane is a flat, two-dimensional surface that extends to infinity, and the flow channel and valve openings are located in the same plane and extend in different directions along the same plane.

[0075] In an embodiment, the overflow fluid is at approximately 1 to 10 bar, preferably approximately 1 to 5 bar, and more preferably approximately 1 to 3 bar.

[0076] In an embodiment, the valve openings are equidistantly distributed around the circumference of the housing, and the valve openings are preferably distributed at an angle of approximately 120 degrees.

[0077] The inner circumference of the housing can be approximately equal to the outer circumference of the valve element.

[0078] The valve element includes a first end and a second end that define a first longitudinal axis. The valve housing includes a first end, a second end, and a second longitudinal axis that extends between the first end and the second end. When the valve is in the assembled configuration, the second longitudinal axis is coaxial with the first longitudinal axis of the valve element.

[0079] In an embodiment, the valve element includes a handle for rotating the valve element inside the valve housing.

[0080] When assembling the safety valve, the valve element can be rotated inside the valve housing, and the rotation is about the second longitudinal axis.

[0081] When a part of the valve element is inserted into the internal spacing, the handle can project from the valve element to the outside of the housing. The handle preferably extends radially from the valve element.

[0082] In an embodiment, the handle includes a first protrusion, a second protrusion, and a third protrusion that extend radially from the valve element. The first protrusion and the second protrusion are preferably arranged in the circumference of the valve element at an angle of 90 degrees relative to each other. The second protrusion and the third protrusion are preferably arranged in the circumference of the valve element at an angle of 90 degrees relative to each other.

[0083] The handle can be a recess that is recessed into the valve element. The recess can be configured to have a shape such as a square, triangle, circle, ellipse, rectangle, star, or any combination thereof.

[0084] In an embodiment, the valve housing further includes a sterile filter element, and the filter is arranged such that any overflow fluid discharged from these overflow depressions passes through the filter element. The filter element can be arranged at the first end and / or the second end of the housing.

[0085] In a further embodiment, the filter covers the entire at least one outlet opening of each of the at least two overflow depressions.

[0086] In a further embodiment, the at least two overflow depressions are arranged in the housing and extend between the first end and the second end of the housing. The at least one outlet opening is arranged in the second end of the housing such that the overflow depressions communicate with the second end of the housing, wherein the filter element is arranged inside the internal spacing at the second end of the housing. Thus, the discharged fluid only leaves the safety valve at the second end of the housing, and thereby all the discharged fluid passes through the sterile filter and then is discharged from the safety valve.

[0087] The filter further prevents any contaminated air from the valve's surrounding environment from entering the safety valve.

[0088] The filter element can have any suitable shape. The filter element can have the same shape as the internal spacing and is preferably circular.

[0089] The filter element can be formed of a material selected from the group consisting of: a porous polymer membrane, sintered particles or fibers made of a polymer, metal or ceramic; or a composition of such materials.

[0090] The filter element can have a pore size of 0.10 μm to 100 μm, preferably 0.2 μm to 0.45 μm.

[0091] The filter element can be a HEPA filter.

[0092] In a fourth aspect, the present invention relates to a safety valve as described in the third aspect above in a method for preparing H 215 Use in a system for preparing and injecting it into a saline solution.

[0093] The system can be the system according to the second aspect described below.

[0094] By providing a safety valve in such a system, if the system fails, i.e., a failure that may cause the fluid in the tube connected to the patient to be at an unwanted high level, the safety valve will protect the patient from being harmed by the unwanted fluid.

[0095] In a second aspect, the invention relates to a system for preparing and injecting H 2 15 O used in positron emission tomography (PET), the system comprising: a production device for producing a saline solution of H 2 15 O; a bolus volume device for establishing a first bolus volume for injection, the first bolus volume comprising the saline solution of H 2 15 O and having a pre-defined volume and radioactivity concentration (mBq / ml), the bolus volume device comprising a valve; and an adjustment device for adjusting the injection profile of the first bolus volume.

[0096] As used herein, the term "oxygen-15 labeled water" is meant to encompass H with similar symbols 2 15 O, such as 015-H2O, O15-H 2 O, H 2 15 O], H 2 O 15 O], and 15 OH 2 O.

[0097] By providing a system according to the invention for preparing and injecting H 2 15 O that can be arranged adjacent to a PET-scanner, the need for manual handling of radioactive isotopes is eliminated, thus enhancing the safety of patients and medical personnel.

[0098] Furthermore, since the system operates continuously, the dose injection can be precisely carried out at the moment of interest. This enables time-critical studies (such as brain activation studies and cardiac stress studies) to be achieved. The system supports various different research protocols by providing different infusion bolus volumes.

[0099] According to the second aspect of the invention, the amount of radioactivity prepared can be precisely determined (since H 2 15 ​O is prepared with a pre-defined bolus volume), and defines and adjusts the injection profile, i.e., the injection rate as a function of time, which defines the amount of radioactivity injected during the injection phase. In some embodiments, the injection rate is constant throughout the injection phase. In this way, the radioactivity and the bolus volume are well defined.

[0100] In some embodiments, the injection rate varies throughout the injection phase.

[0101] As used herein, the term "bolus volume" refers to a specific volume amount.

[0102] As used herein, the term "injection profile" refers to a graph on an XY plot where the Y-axis represents the radioactivity concentration [Bq / s] as a function of time and the X-axis represents time [s].

[0103] In an embodiment, the system according to the second aspect includes a processing unit.

[0104] Herein and hereinafter, the term 'processing unit' is intended to include any circuit and / or device suitable for being adapted to perform the functions described herein. Specifically, the above term includes general-purpose or special-purpose programmable microprocessors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), programmable logic arrays (PLAs), field-programmable gate arrays (FPGAs), special-purpose electronic circuits, etc., or combinations thereof.

[0105] The processing unit may be connected to the production device and / or the bolus volume device and / or the adjustment device and / or the overall system according to the second aspect and / or its specific parts.

[0106] In an embodiment, the valve is a safety valve according to the third aspect of the present invention.

[0107] The system may be connected to a patient such that a bolus volume can be directly injected into the patient from the system. The bolus volume may be administered by intravenous injection, intramuscular injection, intrathecal injection, or subcutaneous injection.

[0108] Multiple parts of the system may be arranged within or behind a radiation protection shield.

[0109] In an embodiment, the present invention relates to a production device for a system according to the second aspect, the production device comprising: converting a gas mixture containing 15 O and H 2 into H 2 15 O at an elevated temperature; a valve control element for regulating the flow rate of the gas mixture; for combining H 2 15 O with brine from a first brine feeder to produce H2 15 Combining device for O salt solutions; first radiation detector for measuring the radioactivity in the H 2 15 O salt solution, wherein the valve control element is regulated by the first radiation detector.

[0110] According to this embodiment, a gas mixture containing 15 O and H 2 is fed to the production device at a constant flow rate and pressure. The provided valve control element can regulate the amount of the gas mixture that is converted into H 2 15 O, and thereby regulate the H 2 15 concentration of H in the O salt solution. 2 15

[0111] The gas mixture can include a compressed or pressurized gas mixture.

[0112] The gas mixture is preferably converted into H in vapor form. 2 15 O.

[0113] The radiation detector can include a control part for comparing the measured radiation amount with a predefined radiation range, the range depending on the desired amount of H in the salt solution. 2 15 O. The range can be input manually and / or automatically according to the desired amount of H. 2 15 O, which can vary according to the patient. The control part can be controlled by a processing unit.

[0114] In an embodiment, the conversion element includes a furnace for converting the gas mixture into H at an elevated temperature. 2 15 O.

[0115] The elevated temperature can be from 200 °C to 1000 °C, preferably approximately 800 °C for non-catalytic reactions, and approximately 300 °C for Pd-catalyzed reactions.

[0116] In an embodiment, the valve control element includes at least one valve for guiding the gas mixture through the conversion element (thereby converting the gas mixture into H). 2 15 O), or bypassing the conversion element when no more H is desired to be produced. 2 15 O (thereby the gas mixture will not be converted into H). 2 ​15 O).

[0117] In a further embodiment, the at least one valve is a two-way valve.

[0118] In a further embodiment, the at least one valve is a safety valve according to the third aspect of the present invention.

[0119] In a further embodiment, the valve control element further includes a third gas waste device. The at least one valve directs the gas mixture to the furnace or bypasses the furnace and the gas is directed into the third gas waste device.

[0120] The third gas waste device may be a slow-leak gas waste device. Alternatively, the third gas waste device may be an external discharge pipe dedicated to discharging the gas mixture.

[0121] In an embodiment, the combining device includes: a reservoir for receiving H 2 15 O and the first salt solution; a second gas waste device for discharging any excess gas from the reservoir; a third pump that is connected to the reservoir at one end and to a decay pipeline at the other end, the decay pipeline being connected to a liquid waste device, wherein the third pump pumps the excess liquid waste from the reservoir through the decay pipeline and into the liquid waste device.

[0122] By providing a combining device that operates without pressurization / at normal pressure, additional safety features are provided to ensure that no gas is dissolved in the radioactive water.

[0123] It should be noted that in the context of the present specification, the term "reservoir" is not limited to a specific reservoir, but may also be other containers having a pre-defined volume, such as a storage tank, basin, storage / deposit element, vessel, or receiver.

[0124] It should be noted that in the context of the present specification, the term "slow-leak gas waste device" refers to a system that allows an excess gas containing a small amount of radioactive isotopes (such as 15 O) to be delayed for an appropriate number of half-lives (preferably at least five half-lives), and then the excess gas is discharged into the open space so that the residual radioactivity is reduced to an acceptable level. The slow-leak gas waste device will typically be located behind a radiation protection screen.

[0125] The second gas waste device may be a slow-leak gas waste device. Alternatively, the second gas waste device may be an external discharge pipe dedicated to discharging excess radioactive gas. Since 15 O has a short half-life and the gas volume involved is small, the radioactivity is almost zero when the gas is discharged.

[0126] comprising 15 O and H 2 The gas mixture containing O and H and fed to the conversion element may contain small amounts of nitrogen oxides (NOx), which are reduced to ammonia (NH 3 ) by reaction with hydrogen. Thus, if ammonia accumulates, the pH of the H 2 15 O salt solution in the reservoir will increase.

[0127] In an embodiment, the combining device further comprises: a first pump connected to the first brine feeder to supply the salt solution to the reservoir; and a pH measuring device connected to the decay line, wherein the first pump is regulated by the pH measuring device.

[0128] The amount of the first salt solution from the first brine feeder can be an adjustable amount. The amount of the first salt solution can be adjusted manually and / or automatically by a processing unit.

[0129] The first salt solution can be continuously pumped into the reservoir.

[0130] By providing a pH measuring device, the device can detect changes in the pH value of the H 2 15 O salt solution. These changes may occur if there is a large amount of ammonia in the H 2 15 O salt solution.

[0131] To ensure that ammonia does not accumulate in the reservoir, the inflow rate of the salt solution and the outflow rate of the H 2 15 O salt solution can be adjusted so that ammonia is flushed out of the reservoir.

[0132] The ammonia content in the reservoir should be less than 15 ppm, preferably less than 10 ppm. The pH level in the reservoir should be from 4 to 10, preferably from 5 to 9, more preferably from 5.5 to 8.5.

[0133] Providing a relatively long decay line allows the radioactive H 2 15 O to reach the waste bottle after decay. Before reaching the waste bottle, the radioactive H 2 15 O will preferably be delayed by at least five half-lives.

[0134] The waste bottle can be placed outside the radiation protection shield arranged around the system. The radiation detector can also be arranged adjacent to the decay line or the waste bottle.

[0135] The pumping speed of P3 is greater than or equal to the pumping speed of P1 to ensure H 215 The reservoir of the O-salt solution does not overflow.

[0136] Any excess gas present in the reservoir is discharged through a second gas waste device, which can be a slow-leak gas waste device.

[0137] In an embodiment, the present invention relates to a bolus dosing device for a system according to the second aspect, wherein the bolus dosing device comprises: a reservoir containing H 2 15 O-salt solution; a delivery tube for circulating the H 2 15 O-salt solution from the reservoir through a loop element and a regulating device and back to the reservoir; a second pump for regulating the flow rate, wherein the regulating device comprises a valve having a first configuration and a second configuration, and wherein the second configuration of the regulating device establishes a first bolus dose of the H 2 15 O-salt solution, the first bolus dose having a pre-defined volume and radioactivity concentration.

[0138] By providing a continuously circulating and readily available H 2 15 O-salt solution, the system is ready at any point in time to establish a first bolus dose for injection into a patient, thereby avoiding unnecessary waiting times.

[0139] The reservoir can contain an H 2 15 O-salt solution produced according to an embodiment of the present invention.

[0140] Furthermore, since the H 2 15 O-salt solution is continuously circulated in the delivery tube from the reservoir and back to the reservoir at high speed by the second pump, newly formed H 2 15 O in the reservoir is continuously mixed with the saline, so that the H 2 15 O-salt solution available in the loop element will maintain a substantially constant radioactivity concentration.

[0141] The speed of the second pump is preferably from 0.1 ml / min to 100 ml / min.

[0142] In an embodiment, the bolus dosing device comprises a processing unit.

[0143] The regulating device can be manually controlled and / or automatically controlled by the processing unit.

[0144] In an embodiment, the regulating device comprises at least two valves.

[0145] In an embodiment, the regulating device includes a safety valve according to the third aspect of the present invention.

[0146] In an embodiment, the at least two valves are arranged on either side of the loop element. One of the two valves may be connected to the patient line.

[0147] By using the safety valve according to the third aspect of the present invention, no overflow liquid will enter the patient line, thus ensuring a safer system.

[0148] In an embodiment, the loop element has an adjustable volume. The volume of the loop element can be adjusted manually and / or automatically by the processing unit. The volume of the loop element can also be adjusted by changing one or more parts of the loop element, thereby giving a different part or parts of the loop element a volume such that the loop element has another volume.

[0149] Therefore, different bolus volumes and radioactive concentrations can be easily provided for different patients and / or measurements, thereby eliminating the need for medical personnel to manually aspirate the bolus.

[0150] In an embodiment, a first radiation detector is arranged adjacent to the loop element. The first radiation detector includes a first detector unit and a second detector unit, wherein the first detector unit and the second detector unit measure a first radioactive value and a second radioactive value of the H 2 15 O salt solution present in the loop element.

[0151] The first detector unit and the second detector unit are preferably arranged at different positions adjacent to the loop element. Thus, these detectors measure the first radioactive value and the second radioactive value of the H 2 15 O salt solution at different positions in the loop element. The first radiation detector can be individually shielded to produce accurate radiation measurement results.

[0152] In a first aspect, the present invention relates to a regulating device for a system according to a second aspect. The regulating device includes: a second saline feeder; a loop element, the loop element including a first bolus of the H 2 15O saline solution; an injection device for collecting a pre-defined second bolus volume of saline from the second saline feeder and injecting the second bolus volume into the loop element at a pre-defined rate such that the second bolus volume pushes the first bolus volume into the patient line; a second radiation detector adjacent to the patient line, the radiation detector measuring the injection profile of the first bolus volume, wherein the injection rate and volume of the second bolus volume condition the injection profile of the first bolus volume.

[0153] By providing the injection device, the injection profile of the first bolus volume injected into the patient line can be conditioned depending on the individual requirements for different measurements.

[0154] In an embodiment, the conditioning device according to the first aspect includes a processing unit.

[0155] The pre-defined injection rate can be changed during the injection. The rate is preferably decreased during the injection. The change in the rate can be controlled manually or by the processing unit.

[0156] Depending on different patients and measurements, the pre-defined second bolus volume of saline can have a variable volume. The pre-defined second bolus volume can be collected manually and / or automatically by the injection device. The automatic collection can be controlled by the processing unit.

[0157] In an embodiment, the injection device includes a fourth valve. The fourth valve can be a safety valve according to the third aspect of the present invention.

[0158] The second saline feeder can be connected to the fourth valve.

[0159] In an embodiment, the injection device includes a collection element. The collection element can be connected to the fourth valve. The collection element can be a medical syringe.

[0160] The second detector measures the radioactivity value of a specific portion of the patient line. This portion has a known length, size, and volume. Since the volume of this portion of the patient line is constant, the radioactivity is measured at short time intervals (1 to 10 measurements per second), and the injection rate is known, so a curve (herein referred to as the injection profile) can be obtained in the XY coordinate system that shows the amount of injection activity over time.

[0161] The second radiation detector measures the injection profile of the first bolus volume immediately before the first bolus volume is injected into the patient.

[0162] In a fifth aspect, the present invention relates to a method for preparing H for use in positron emission tomography 2 15The method of O, the method comprising the steps of: at an elevated temperature, a gas mixture comprising 15 O and H 2 is converted into H 2 15 O; providing a valve control element to regulate the flow rate of the gas mixture; combining H 2 15 O with brine from a first brine feeder to produce a H 2 15 O salt solution; providing a first radiation detector to measure the radioactivity in the H 2 15 O salt solution; regulating the flow rate of the gas mixture by means of the first radiation detector; providing a reservoir to receive the H 2 15 O salt solution; providing a second gas waste device for discharging any excess gas from the reservoir; providing a third pump which is connected to the reservoir at one end and to a decay pipeline at the other end, the decay pipeline being connected to a liquid waste device; pumping any excess liquid waste from the reservoir through the decay pipeline and into the liquid waste device by means of the third pump; providing a delivery pipe and a second pump to circulate the H 2 15 O salt solution from the reservoir through a loop element and back to the reservoir; providing a regulating device; establishing a first bolus of the H 2 15 O salt solution in the loop element, the first bolus having a pre - defined volume and radioactivity concentration; providing a second brine feeder; collecting a pre - defined second bolus of brine from the second brine feeder; injecting the second bolus into the loop element at a pre - defined rate such that the second bolus pushes the first bolus into a patient pipeline; measuring the injection curve value of the first bolus with a second radiation detector adjacent to the patient pipeline, thereby regulating the injection curve of the first bolus by means of the injection rate and volume of the second bolus.

[0163] In an embodiment of the fifth aspect, the regulating device comprises a safety valve according to the third aspect of the present invention.

[0164] Generating and injecting a radioactive isotope into a patient system presents several challenges. The safety requirements for such systems that can be connected to a patient are extremely high to ensure the safety of the patient and medical staff. By providing a system according to the second aspect, different parts of the system help ensure a higher safety standard than previously possible.

[0165] The safety valve according to the third aspect is particularly useful in the system according to the second aspect, as it will prevent the overflow fluid from moving forward in the system and ultimately entering the patient's body. In particular, excessive gas is a very high-risk factor, and this risk can be easily eliminated by implementing the safety valve according to the third aspect.

[0166] The different aspects of the present invention can be implemented in different ways, each of which produces one or more benefits and advantages described in connection with at least one of the aspects described above, and each has one or more preferred embodiments, including the embodiments described in connection with at least one of the aspects disclosed above and / or in the dependent claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0167] The above and / or additional objects, features, and advantages of the present invention will be further elaborated by the following illustrative and non-limiting detailed description of embodiments of the present invention with reference to the accompanying drawings, in which:

[0168] Figure 1 A schematic diagram of a system for preparing and injecting H 2 15 O used in positron emission tomography is shown.

[0169] Figure 2 is a flowchart showing the interaction between the bolus device and the injection device.

[0170] Figure 3A and Figure 3B show embodiments according to the second aspect and the first aspect of the present invention.

[0171] Figure 4A and Figure 4B show different injection curves for a first bolus.

[0172] Figure 5 A perspective view of an embodiment of a safety valve according to the second aspect of the present invention is shown.

[0173] Figure 6 shows Figure 5 a perspective view of the safety valve shown in the assembled configuration.

[0174] Figure 7A 、 Figure 7B 、and Figure 7C show cross-sectional views of the assembled safety valve in a first assembled configuration, a second assembled configuration, and a third assembled configuration.

[0175] Figure 8 A perspective view of an embodiment of a valve according to the third aspect of the present invention is shown.

[0176] Figure 9 shows Figure 8 a cross-sectional view of the safety valve shown when in the assembled position. DETAILED DESCRIPTION

[0177] In the following description reference is made to the accompanying drawings which show by way of illustration how the invention may be practiced. It should be noted that for purposes of illustration, in particular the dimensions of the distances between the various different elements shown are not to scale.

[0178] It is to be understood that the terms "safety valve" and "valve" are both used in the context of the present invention to describe the safety valve according to the third aspect of the present invention.

[0179] Figure 1 shows a schematic diagram of a system 1 embodying the present invention for preparing H 2 15 O in a sterile injectable form for use in a PET scan.

[0180] System 1 includes a processing unit for controlling the various different parts of the system. If desired, the processing unit may be manually rewritten.

[0181] Herein and hereinafter, the term 'processing unit' is intended to include any circuit and / or device adapted to perform the functions described herein. In particular, the above term includes general or special purpose programmable microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), programmable logic arrays (PLAs), field programmable gate arrays (FPGAs), dedicated electronic circuits, etc., or combinations thereof.

[0182] Radioactive 15 O gas is typically produced in a cyclotron in cyclotron vault 500 by irradiating a flowing gas target of nitrogen and oxygen. 15 The amount of 15 O gas released from cyclotron target chamber 501 is controlled by a mass flow controller (MFC) (not shown) positioned in connection with target chamber 501. The MFC is preset to control the gas within a specific flow rate range.

[0183] The MFC is equipped with a closed-loop control system which takes an input signal from the system operator or the processing unit, compares the input signal with the value from the mass flow sensor, and adjusts the proportional valve accordingly to achieve the desired flow rate.

[0184] Then 2 O gas passes through a NOx trap 502 where most of the nitrogen oxides formed in target chamber 501 due to the reaction between nitrogen and oxygen, such as NO, N 2。At this time, it is desirable to remove nitrogen oxides because they may subsequently be converted to unwanted ammonia (NH 3 ) by reacting with hydrogen.

[0185] Subsequently, the gas is mixed with hydrogen (H 2 ) from the hydrogen reservoir 503 to form a gas mixture 221 of H 2 and 15 O gas. The amount of H 15 gas mixed with 2 O gas is controlled by another MFC (not shown) located behind the hydrogen reservoir 503.

[0186] Then, the gas mixture 221 is guided through a tube 504 extending from the cyclotron vault 500 and into the PET scan chamber 505, where the PET scanner (not shown), the patient 521, and the present invention according to the second aspect are arranged. To avoid high pressure that may cause unstable flow rates, the tube 504 is equipped with a pressure relief valve (not shown).

[0187] Then, the gas mixture 221 passes through a first sterile filter 506 to remove any unwanted particles and microbial impurities, thereby ensuring that the system remains sterile.

[0188] Behind the first sterile filter 506, a pressure sensor 507 and a pressure relief valve 508 are connected to the gas delivery tube 504. The pressure sensor 507 continuously measures the pressure in the tube 504. If the pressure exceeds a predetermined safety level, the valve 508 directs the gas mixture 221 to a first gas waste device 509.

[0189] The gas mixture 221 is then directed to a tube node 510. A valve control element 250 controls the way the gas mixture 221 is directed from the tube node 510. The valve control element 250 includes a second valve 251 and a third valve 252.

[0190] When the second valve 251 is open, the gas 221 is directed through a conversion element 220. The conversion element 220 is a furnace 220 in which the gas mixture 221 is converted to H 2 15 O. If the second valve 251 is closed and the third valve 252 is open, the gas mixture 221 will bypass the furnace 220 and the gas mixture 221 will not be converted to H 2 15 O. This is achieved when no more H 2 15 O is desired.

[0191] The gas mixture 221 from the third valve 252 and / or the H2 15 O is then directed into reservoir 281. A first pump 292 connected to the first brine feeder 290 continuously pumps a first brine stream 291 into reservoir 281. Thus, H 2 15 O and brine are combined in reservoir 281 to form an H 2 15 O brine solution.

[0192] A first radiation detector 240 is positioned at other locations in the system. The first radiation detector 240 measures the radioactivity in the H 2 15 O brine solution. The signal from the first radiation detector 240 is used as an input in a closed-loop regulation algorithm, such as PID or fuzzy logic executed on a processing unit. The output from the processing unit regulates the valve control element 250 and thus determines how much H 2 15 O is produced.

[0193] A second gas waste device 282 is connected to reservoir 281. The second gas waste device 282 discharges the gas from the reservoir 281, thus ensuring that no gas is dissolved in the H 2 15 O brine solution.

[0194] A third pump 283 is connected to reservoir 281 at one end and to a decay line 284 at the other end. The decay line 284 is further connected to a liquid waste device 285. The third pump 283 continuously pumps the excess liquid waste from reservoir 281 through the decay line 284 and into the liquid waste device 285.

[0195] Reservoir 281 is also connected to a delivery pipe 301 to circulate the H 2 15 O brine solution from reservoir 281 and return it to reservoir 281. The H 2 15 O brine solution is pumped from reservoir 281 by a second pump 302 into the delivery pipe 301 and into a regulating device 340 and a loop element 320.

[0196] The regulating device 320 includes a fifth valve 422 and a sixth valve 423, which are valves as shown in Figure 5 FIGS. 6 to 7. The valves 422, 423 are arranged on each side of the loop element 320. A fifth valve 424 is further connected to an injection device 420, and a sixth valve 425 is further connected to a patient line 520.

[0197] The fifth valve 424 is arranged in a first configuration of at least two different configurations such that H2 15 The O salt solution flows through the fifth valve 424 and is directed into the loop, and the injection device 420 is isolated from the rest of the system. If the fifth valve 424 is arranged in the second configuration, then H 2 15 the O salt solution will not be able to flow through the fifth valve 424, and the fifth valve 424 disconnects the connection between the loop 320 and the injection device 420.

[0198] The sixth valve 425 is arranged in a first configuration of at least two different configurations such that H 2 15 the O salt solution flows through the sixth valve 425, and is further directed into the delivery tube 301 and returns to the reservoir 281. If the sixth valve 425 is arranged in the second configuration, then H 2 15 the O salt solution will be directed into the patient line 520, and that part of the delivery tube 301 that returns the H 2 15 O salt solution transported back to the reservoir 281 is isolated from the sixth valve 425.

[0199] The first radiation detector 240 is arranged adjacent to the loop element 320. The first radiation detector 240 includes a first detector unit and a second detector unit (not shown), wherein the first detector unit and the second detector unit measure the first radioactivity value and the second radioactivity value of the H 2 15 O salt solution present in the loop element 320.

[0200] If the first radioactivity value and the second radioactivity value deviate from the user preset threshold level by more than 20%, preferably 15%, more preferably 10%, the processing unit will prevent the injection from occurring.

[0201] When the fifth valve 422 and the sixth valve 423 are arranged in the second configuration, the fifth valve 424, the sixth valve 425, and the loop element 320 establish the H 2 15 O salt solution of the first bolus volume. The first bolus volume has a predefined volume and radioactivity concentration.

[0202] The injection device 420 includes a fourth valve 422 and a collection element 423. The collection element 420 is a medical syringe 420. The fourth valve 422 is the valve as Figures 5 to 8 shown. The medical syringe 420 can be manually controlled and / or automatically controlled by the processing unit. The second saline feeder 401 is connected to the fourth valve 423.

[0203] The fourth valve 423 is arranged in a first configuration of at least two different configurations such that the connection between the medical syringe 422 and the fifth valve 424 is disconnected. If the fourth valve 423 is arranged in a second configuration, the connection between the medical syringe 422 and the second saline feeder 401 will be disconnected.

[0204] When the fourth valve 423 is in the second configuration, the medical syringe 422 can collect a pre-defined second bolus volume of saline from the second saline feeder 401.

[0205] The patient line 520 connected to the sixth valve 425 is also connected to a bubble detector 522, a check valve 523, a second sterile filter 524, and a patient 521.

[0206] The bubble detector 522 detects the presence of any unwanted bubbles in the first bolus volume and / or the second bolus volume. In the event of an unwanted event of detecting bubbles, the processing unit connected to the bubble detector 522 stops the injection to the patient.

[0207] The check valve 523 is a one-way valve. The valve 523 ensures that the first bolus volume and / or the second bolus volume that has passed through the valve 523 cannot flow back into the system. Similarly, any fluid from the patient 521 cannot cross the check valve 523 and flow back into the system.

[0208] The second sterile filter 524 removes any unwanted particulate and microbial impurities that may remain, thus ensuring that the first bolus volume and / or the second bolus volume is sterile before entering the patient 521.

[0209] A second radiation detector 440 arranged adjacent to the patient line measures the injection profile of the first bolus volume.

[0210] The patient 521 can be placed in a scanner such as a positron emission tomography (PET) scanner (not shown), where the distribution of the radioisotope in the patient 521 can be monitored before, during, and after the injection of the first bolus volume.

[0211] Figure 2 is a flowchart showing the interaction of the bolus volume device and the injection device to provide an injectable H 2 15 O saline solution with a pre-defined volume and radioactivity concentration.

[0212] In part A, a second pump 302 connected to the delivery tube 301 regulates the flow rate of the H 2 15 O saline solution such that the H 2 15The O salt solution is continuously pumped from reservoir 281 through delivery tube 301, loop element 320, and regulating device 340, thereby providing readily available H in loop element 320 at any given time 2 15 O salt solution.

[0213] The regulating device 340 includes a fifth valve 424 and a sixth valve 425 in a first configuration and arranged on each side of the loop element 320.

[0214] The first radiation detector 240 is arranged adjacent to the loop element 320. The first radiation detector 240 includes a first detector unit and a second detector unit, and the first detector unit and the second detector unit measure the first radioactivity value and the second radioactivity value of the H 2 15 O salt solution present in the loop element 320.

[0215] When the radioactivity in the loop element 320 reaches a desired level, which can vary between different measurements and between different patients, part B starts automatically or manually.

[0216] In part B, the fifth valve 424 and the sixth valve 425 are changed from the first configuration to the second configuration such that the loop element 320 is not connected to the delivery tube 301 and the part of the system that produces the H 2 15 O salt solution. Additionally, the patient 521 is also isolated from the rest of the system.

[0217] The fifth valve 424 and the sixth valve 425 can be changed in configuration simultaneously or individually. The second configuration of the fifth valve 424 and the sixth valve 425 establishes the first bolus dose of the H 2 15 O salt solution, and the first bolus dose is the amount of the H 2 15 O salt solution present in the loop element 320. Thus, the first bolus dose has a pre - defined volume and a radioactivity concentration, which is measured by the first detector unit and the second detector unit.

[0218] The loop element 320 has an adjustable volume, which can be changed between different patients and different measurements.

[0219] In the second configuration, the sixth valve 425 is connected to the patient line 520, and the fifth valve 424 is connected to the fourth valve 422.

[0220] In part C, the fourth valve 422 is connected to the second brine feeder 401 and the collection element 423. When the fourth valve 422 is in the first configuration, the connection between the collection element 423 and the fifth valve 424 is disconnected.

[0221] When the fourth valve 422 is switched to the second configuration, the connection between the collection element 423 and the second brine feeder 401 is disconnected.

[0222] In part D, the collection element 423 aspirates a desired amount of brine from the second brine feeder 401, thereby establishing a second bolus volume of brine. The second bolus volume of brine is preferably 5 ml to 150 ml, more preferably 10 ml to 100 ml.

[0223] In part E, the fourth valve 422 is switched to the first configuration, thereby establishing a connection between the collection element 423 containing the second bolus volume of brine and the fifth valve 424.

[0224] In part F, the fourth valve 422, the fifth valve 424, and the sixth valve 425 are arranged in the first configuration. The collection element 423 injects the second bolus volume of brine into the loop element 320.

[0225] In part G, the velocity of the second bolus volume will push the first bolus volume of H 2 15 O saline solution present in the loop element 320 and the second bolus volume itself into the patient line 520 and ultimately into the patient 521. The injection rate and volume of the brine regulate the injection profile of the second bolus volume into the patient 521.

[0226] The second radiation detector 440 adjacent to the patient line 520 measures the injection profile of the first bolus volume.

[0227] In the above Figure 2 All parts from A to G in the description can be started and executed manually and / or automatically by the processing unit. The start of a certain part also depends on the termination of another part.

[0228] Figure 2 An exemplary arrangement of the various different parts is shown. Parts C and D (where the second bolus volume of brine is established) can also be performed before part B (where the first bolus volume of H 2 15 O saline solution) is established.

[0229] Figure 3A and Figure 3B shows another embodiment according to the first aspect of the present invention.

[0230] The reservoir 281 includes H 215 O salt solution. The second pump 302 pumps H 2 15 O salt solution from the reservoir 281 is continuously pumped into the delivery tube 301, through the regulating device 340 and the loop element 320, and back to the reservoir 281.

[0231] The regulating device 340 includes a plurality of safety valves according to the third aspect of the present invention. In Figure 3A and Figure 3B , the plurality of valves are shown as 7 valves.

[0232] In Figure 3A , the regulating device 340 is in a first configuration, in which H 2 15 O salt solution is pumped through the loop element 320. The injection device 420 is also in a first configuration, in which a second bolus volume of saline is established.

[0233] In Figure 3B , the regulating device 340 is in a second configuration, in which a second bolus volume is established and the connection from the loop element 320 to the patient line 520 is disconnected. The injection device 420 is also in a second configuration, in which the second bolus volume of saline can be injected into the loop element 320, and the first bolus volume and the second bolus volume can enter the patient line 520.

[0234] Figure 4A And B show different injection curves for the first bolus volume.

[0235] When adjusting the injection curve of the first bolus volume (also known as bolus volume modulation), there are two external parameters that can be used to affect the injection curve, namely the injection speed and the bolus volume.

[0236] According to the present invention, the volume of the first bolus volume is determined by the volume of the loop element 320. The volume of the loop element 320 can be changed depending on a specific patient or the measured desired bolus volume.

[0237] According to the present invention, the injection speed is determined by the injection device 420. The injection speed can be changed depending on a specific patient or the measured desired speed.

[0238] These parameters can be changed manually and automatically.

[0239] Furthermore, radioactivity is measured by a second radiation detector (not shown). Accurate measurements can only be made within a specific measurement window in which the radioactivity level is within a certain range. This range, and thus the measurement window, can vary depending on the different types of measurements performed.

[0240] Most commonly, the injection is performed at a uniform injection rate, resulting in an injection curve as shown in Figure 4A the injection curve shown.

[0241] A uniform injection rate results in an injection curve with a sharp peak. The sharp peak limits the time period during which the radioactivity level is within the measurement window and thus limits the time period during which the second radiation detector can measure radioactivity based on the first injection curve.

[0242] In contrast, if the injection is started at a slightly higher injection rate (which then decreases during the injection process), the injection curve as shown in Figure 4B is more evenly distributed in the region of interest, thereby providing an injection curve in which the radioactivity level persists for a longer time period within the measurement window compared to the injection curve with a uniform rate shown in Figure 4a.

[0243] As the radioactivity level persists for a longer time period in the desired measurement window, for example, there can be a longer time period for the PET scanner to accumulate data.

[0244] Furthermore, the ability to modulate the injection curve is very useful during examinations related to cardiac studies, where the injection bolus volume should neither be too steep nor too wide relative to the patient's pulse. A too-steep curve will result in too few available data points in the available window. A too-wide curve will result in the inability to determine parameters necessary for cardiac studies, such as different centroid times.

[0245] In Figure 5 a valve 100 before being assembled into an assembled valve 100 is shown. The valve includes a valve element 120, a valve housing 150, and three overflow recesses 180A, B, C.

[0246] The valve element 120 includes a first end 122 and a second end 123. The first end 122 and the second end 123 define a first longitudinal axis 124. The valve element 120 is cylindrical. A flow channel 121 extends through the valve element 120 generally perpendicular to the first longitudinal axis 124.

[0247] The valve housing 150 is cylindrical and includes a cylindrical outer shell 156. The outer shell 156 includes a first end 157, a second end 158, and a second longitudinal axis 159 extending between the first end and the second end. When the valve is in the assembled configuration, the second longitudinal axis 159 is coaxial with the first longitudinal axis 124 of the valve element 120.

[0248] The valve housing 150 further includes an internal spacing 165 enclosed by the outer housing 156, and includes a first valve opening, a second valve opening, and a third valve opening 151A, B, C. Each valve opening 151A, B, C allows fluid to flow into or out of the outer housing 156. The valve openings 151A, B, C are equidistantly distributed at approximately 120-degree angles to each other along the circumferential direction 160 of the outer housing.

[0249] The valve element 120 is axially movable along a second longitudinal axis 159 such that the second end and a portion of the valve element 120 can be inserted into the internal spacing 165 of the valve housing 150 to form the assembled valve 100.

[0250] The valve element 120 includes, at the first end, a handle for rotating the valve element 120 inside the valve housing 150. The handle includes a first protrusion, a second protrusion, and a third protrusion 125A, B, C arranged in the outer circumference 126 of the valve element 120, and these protrusions 125A, B, C extend radially from the valve element 120. The first protrusion and the second protrusion 125A, B are arranged at a 90-degree angle to each other. The second protrusion and the third protrusion 125B, C are arranged at a 90-degree angle to each other. The first protrusion and the third protrusion 125A, C are arranged at a 180-degree angle to each other. These protrusions 125A, B, C have a rectangular shape.

[0251] The valve housing 150 includes a first hollow connecting element, a second hollow connecting element, and a third hollow connecting element 152A, B, C. Each connecting element 152A, B, C has: a first end 153A, B, C; a second end 154A, B, C; and an internal fluid space 155A, B, C. The connecting elements 152A, B, C are connected to the valve housing 150 at the second ends 154A, B, C such that the fluid spaces 155A, B, C are in fluid contact with the three valve openings 151A, B, C.

[0252] Three linear overflow recesses 180A, B, C are arranged in the valve housing 150, more precisely, these overflow recesses 180A, B, C are arranged in the outer housing 156. Each overflow recess 180A, B, C axially extends between the first end 157 and the second end 158 of the outer housing 156. Each overflow recess 180A, B, C has a first outlet opening and a second outlet opening 181A, B. The overflow recesses 180A, B, C are equidistantly distributed at approximately 120-degree angles to each other along the circumferential direction 160 of the outer housing.

[0253] Figure 6 A perspective view of the assembled valve 100 is shown.

[0254] The valve element 120 is arranged inside the internal spacing 165. The valve element 120 is rotatable within the internal spacing 165 about a second longitudinal axis 159 such that the valve element 120 and the valve housing 150 can change between at least three different open configurations 100A, B, C, namely Figure 7A , Figure 7B , and Figure 7C the first open configuration, the second open configuration, and the third open configuration as shown.

[0255] The valve housing 150 includes a circular bottom plate 162. The bottom plate 162 is connected to and extends across the second end 158 of the outer housing 156 such that the bottom plate 162 closes the internal spacing 165 at the second end 158.

[0256] These three outlet openings 181B of the overflow recesses 180A, B, C are arranged in the bottom plate 162 such that excess fluid can be discharged through the bottom plate 162 via the overflow recesses 180A, B, C.

[0257] Figure 7A , Figure 7B and Figure 7C show cross-sectional views of the assembled valve in a first assembled configuration, a second assembled configuration, and a third assembled configuration.

[0258] In Figure 7A -C, a first connection element, a second connection element, and a third connection element 152A, B, C are connected to a first valve opening, a second valve opening, and a third valve opening 151A, B, C.

[0259] The valve element 120 and the valve housing are in contact with each other in three contact regions 101A, B, C. More precisely, the outer circumference 126 of the valve element 120 is adjacent to the inner circumference 161 of the outer housing 156 of the valve housing 156 in these three contact regions 101A, B, C. Each of these contact regions 101A, B, C forms a fluid stop 103.

[0260] Each overflow recess 180A, B, C is arranged between the valve element 120 and the valve housing 150. These overflow recesses 180A, B, C are not in fluid communication with the flow channel 121.

[0261] The first overflow recess 180A is positioned to create an interruption in the first contact region 101A. The second overflow recess 180B is positioned to create an interruption in the second contact region 101B. The third overflow recess 180C is positioned to create an interruption in the third contact region 101C.

[0262] Each overflow recess 180A, B, C creates an interruption of the contact areas 101A, B, C such that each overflow recess 180A, B, C creates a safe release opening for discharging overflow fluid which, in case of overpressure, passes through the fluid stop 103 via the respective outlet openings 181A, B (not shown).

[0263] In Figure 7A is shown an assembled valve 100 in a first assembled open configuration. The first valve opening and the second valve opening 151A, B are connected by a flow channel 121. The third valve opening 151C is not connected to the flow channel 121.

[0264] The first assembled open configuration 100A has a flow path 102 through the first connecting element and the second connecting element 152A, B, the flow channel 121, and the first valve opening and the second valve opening 151A, B.

[0265] The second contact area and the third contact area 101B, C each form a fluid stop 103 which prevents fluid flow into the third valve opening 151C which is not connected to the flow channel 121. If any fluid passes through the fluid stop 103 in the second contact area 101B, the fluid will be discharged via the second overflow recess 180B. If any fluid passes through the fluid stop 103 in the third contact area 101C, the fluid will be discharged via the third overflow recess 180C.

[0266] In Figure 7B is shown an assembled valve 100 in a second assembled open configuration. The second valve opening and the third valve opening 151B, C are connected by a flow channel 121. The first valve opening 151A is not connected to the flow channel 121.

[0267] The second assembled open configuration 100B has a flow path 102 through the second connecting element and the third connecting element 152B, C, the flow channel 121, and the second valve opening and the third valve opening 151B, C.

[0268] The first contact area and the third contact area 101A, B each form a fluid stop 103 which prevents fluid flow into the first valve opening 151A which is not connected to the flow channel 121. If any fluid passes through the first stop 103 in the first contact area 101C, the fluid will be discharged via the first overflow recess 180C. If any fluid passes through the fluid stop 103 in the second contact area 101B, the fluid will be discharged via the second overflow recess 180B.

[0269] In Figure 7CIn [description], the assembled valve 100 in the third assembled open configuration is shown. The first valve opening and the third valve openings 151A, C are connected by a flow channel 121. The second valve opening 151B is not connected to the flow channel 121.

[0270] The third assembled open configuration 100C has a flow path 102 passing through the first connecting element and the third connecting elements 152A, C, the flow channel 121, and the first valve opening and the third valve openings 151A, C.

[0271] The first contact area and the second contact areas 101A, B each form a fluid block 103 that prevents fluid flow from entering the first valve opening 151A not connected to the flow channel 121. If any fluid passes through the first block 103 in the first contact area 101C, the fluid will be discharged through the first overflow recess 180C. If any fluid passes through the fluid block 103 in the second contact area 101B, the fluid will be discharged through the second overflow recess 180B.

[0272] In Figure 7A and Figure 7C a plane P is shown. The valve openings 151A, B, C and the flow path 121 are arranged in the same plane P and extend along the plane P.

[0273] When the valve is in the assembled configuration, the plane P is substantially perpendicular to the first axis 124 and the second axis 159 ( Figure 5 as shown).

[0274] In Figure 8 and Figure 9 embodiments of a safety valve according to the third aspect of the present invention in the unassembled position and the assembled position are shown respectively. This embodiment is constructed corresponding to the embodiment shown in Figure 5 to FIG. 7, with the difference that:

[0275] The valve element 120 has three flow channels 121A, B, C, and each flow channel extends through the valve element 120.

[0276] The valve housing 150 has six valve openings 151A, B, C, D, E, F. Each valve opening 151A, B, C, D, E, F allows fluid to flow into or out of the housing 156. The valve openings 151A, B, C, D, E, F are equidistantly distributed at approximately 60-degree angles to each other along the circumferential direction 160 of the housing. The valve housing 150 has six hollow connecting elements 152A, B, C, D, E, F.

[0277] The valve includes six overflow recesses 180A, B, C, D, E, F. These overflow recesses are equidistantly distributed at approximately 60-degree angles to each other along the circumferential direction 160 of the housing.

[0278] The assembled valve 100 can be changed among six different open configurations 100A, B, C, where: in one open configuration, three flow paths 102A, B, C are defined through three flow channels 121A, B, C and three sets of the valve openings; and in another configuration among the open configurations, three different flow paths 102D, E, F are defined through three flow channels 121A, B, C and three different additional sets of the valve openings; and in a third configuration among the open configurations, three different flow paths 102G, H, I are defined through flow channels 121A, B, C and yet another three different additional sets of the valve openings.

[0279] The following items are embodiments of the present invention:

[0280] 1. A valve 100 for controlling the flow rate of H 2 15 O used in positron emission tomography, the valve 100 comprising:

[0281] A valve element 120 having a flow channel 121 extending therethrough,

[0282] A valve housing 150 having at least three valve openings 151A, B, C, each valve opening 151A, B, C allowing fluid to flow into or out of the valve 100, and

[0283] At least two overflow recesses, each overflow recess having at least one outlet opening,

[0284] Wherein the valve element 120 and the valve housing 150 can be connected to form an assembled valve 100, and the valve element 120 and the valve housing 150 are in contact with each other in the contact area,

[0285] Wherein the assembled valve 100 can be arranged in at least two different configurations, one of the configurations defining a flow path through the flow channel 121 and a set of the valve openings, and another configuration among the configurations defining a flow path through the flow channel 121 and another different set of the valve openings, and

[0286] Wherein in each of the at least two configurations:

[0287] - Each overflow recess is arranged between the valve element 120 and the valve housing 150,

[0288] - At least two of the valve openings are connected by the flow channel 121,

[0289] - At least one of the valve openings is not connected to the flow channel 121,

[0290] - The contact area forms a fluid barrier that prevents fluid from flowing into the at least one valve opening not connected to the flow channel 121.

[0291] - These overflow recesses are not in fluid communication with the flow channel 121.

[0292] - Each overflow recess is positioned to create an interruption in the contact area such that the overflow recesses create a safe release outlet for discharging overflow fluid, and in the case of overpressure, the overflow fluid passes through the fluid barrier through the corresponding outlet opening, so that in the at least two configurations, the overflow fluid is prevented from entering the at least one valve opening not connected to the flow channel 121.

[0293] 2. The valve 100 according to item 1, wherein the valve housing 150 further includes a connecting element having a first end, a second end, and an internal fluid space, and the connecting element is connected to the valve housing 150 at the second end such that the fluid space is in fluid contact with one of the at least three valve openings 151A, B, C.

[0294] 3. The valve 100 according to item 1 or 2, wherein the at least two overflow recesses are arranged in the valve housing 150 and / or the valve element 120.

[0295] 4. The valve 100 according to any one of the foregoing items, wherein

[0296] The valve element 120 further includes a first end and a second end defining a first longitudinal axis, and

[0297] The valve housing 150 further includes:

[0298] - A housing that includes a first end, a second end, and a second longitudinal axis extending between the first end and the second end, and the second longitudinal axis is coaxial with the first longitudinal axis.

[0299] - An internal spacing for receiving the valve element 120, and the internal spacing is enclosed by the housing, and

[0300] - The at least three valve openings 151A, B, C arranged in the housing, and each opening allows fluid to flow into or out of the internal spacing.

[0301] Wherein the at least two overflow recesses axially extend between the first end and the second end of the housing.

[0302] wherein the valve element 120 is axially movable along the second longitudinal axis such that a portion of the valve element 120 can be inserted into the internal spacing of the valve housing 150 to form an assembled configuration, and the valve element 120 is rotatable about the second longitudinal axis within the internal spacing such that the valve element 120 and the valve housing 150 are capable of changing between the at least two different configurations,

[0303] wherein when the valve element 120 is arranged inside the internal spacing in the two different configurations, each overflow recess is arranged between the valve element 120 and the outer housing.

[0304] 5. The valve 100 according to any one of the preceding items, wherein the valve housing 150 includes three valve openings 151A, B, C, and / or the valve includes 3 overflow recesses, and / or the valve element 120 includes a flow channel 121.

[0305] 6. The valve 100 according to any one of the preceding items, wherein the at least two overflow recesses are arranged in the outer housing, and / or the at least two overflow recesses extend between the first end and the second end of the outer housing and open into the first end and / or the second end, and / or the at least two overflow recesses extend between the first end and the second end of the valve element 120 and open into the first end and / or the second end.

[0306] 7. The valve 100 according to any one of the preceding items, wherein the outer housing is cylindrical, and / or the valve element 120 is cylindrical, and / or the valve openings are distributed equidistantly around the circumference of the outer housing, and the valve openings are preferably distributed at an angle of approximately 120 degrees to each other in the circumferential direction.

[0307] 8. A system for preparing and injecting H 2 15 O for use in positron emission tomography, the system comprising:

[0308] - a production device for producing an H 2 15 O salt solution,

[0309] - a bolus dose device for establishing a first bolus dose for injection, the first bolus dose comprising the H 2 15 O salt solution and having a pre-defined volume and radioactivity concentration, the bolus dose device comprising a valve 100, and

[0310] - an adjustment device for adjusting the injection profile of the first bolus dose.

[0311] 9. A production device for the system according to item 8, the production device comprising:

[0312] - Convert a gas mixture 221 containing 15 O and H 2 into H 2 15 O conversion element,

[0313] - A valve control element 250 for regulating the flow rate of the gas mixture 221,

[0314] - For combining H 2 15 O with brine from a first brine feeder to produce H 2 15 O salt solution merging device,

[0315] - A first radiation detector 240 for measuring the radioactivity in the H 2 15 O salt solution,

[0316] wherein the valve control element 250 is regulated by the first radiation detector 240.

[0317] 10. The production device according to item 9, wherein the merging device includes:

[0318] - A reservoir 281 for receiving H 2 15 O and the first salt solution,

[0319] - A second gas waste device for discharging any excess gas from the reservoir 281,

[0320] - A third pump, which is connected to the reservoir 281 at one end and to a decay pipeline at the other end, and the decay pipeline is connected to a liquid waste device,

[0321] wherein the third pump pumps excess liquid waste from the reservoir 281 through the decay pipeline and into the liquid waste device,

[0322] and / or the merging device further includes:

[0323] - A first pump, which is connected to the first brine feeder to supply the salt solution to the reservoir 281, and

[0324] - A pH measuring device connected to the decay pipeline,

[0325] wherein the first pump is regulated by the pH measuring device.

[0326] 11. A bolus dosing device for the system according to item 8, wherein the bolus dosing device includes:

[0327] -Contains H 2 15 O salt solution reservoir 281,

[0328] - A delivery pipe 301, which is used to make the H 2 15 O salt solution circulates from the reservoir 281 through the loop element 320 and the regulating device 340 and returns to the reservoir 281,

[0329] - a second pump 302 for regulating said flow rate,

[0330] The regulating device 340 includes a valve, and the regulating device 340 has a first configuration and a second configuration, wherein the second configuration of the regulating device 340 establishes the H of the first bolus amount. 2 15 O saline solution, the first bolus having a predefined volume and radioactivity concentration.

[0331] 12. The bolus device according to item 11, wherein the valve is a valve according to any one of items 1 to 5, and / or

[0332] The loop element 320 has an adjustable volume, and / or

[0333] The first radiation detector 240 is arranged adjacent to the loop element 320, and the first radiation detector 240 includes a first detector unit and a second detector unit, wherein the first detector unit and the second detector unit measure the H present in the loop element 320. 2 15 O salt solution with a first radioactivity value and a second radioactivity value.

[0334] 13. A regulating device for the system according to item 8, the regulating device comprising:

[0335] - a second brine feeder 401,

[0336] - a loop element 320, which includes the H of the first bolus amount 2 15 O salt solution,

[0337] an injection device 420 for collecting a predefined second bolus amount of saline from the second saline feeder 401 and injecting the second bolus amount into the loop element 320 at a predefined rate so that the second bolus amount pushes the first bolus amount into the patient line 520,

[0338] a second radiation detector 440 adjacent to the patient line 520, said radiation detector measuring an infusion profile of said first bolus amount,

[0339] wherein the injection rate and volume of the second bolus dose regulate the injection profile of the first bolus dose.

[0340] 14. A method for preparing H 2 15 O for use in positron emission tomography, the method comprising the steps of:

[0341] - converting a gas mixture 221 comprising 15 O and H 2 into H 2 15 O at an elevated temperature,

[0342] - providing a valve control element 250 to regulate the flow rate of the gas mixture 221,

[0343] - combining H 2 15 O with saline from a first saline feeder to produce a H 2 15 O saline solution,

[0344] - providing a first radiation detector 240 to measure the radioactivity in the H 2 15 O saline solution,

[0345] - regulating the flow rate of the gas mixture 221 by means of the first radiation detector 240,

[0346] - providing a reservoir 281 to receive the H 2 15 O saline solution,

[0347] - providing a second gas waste device for discharging any excess gas from the reservoir 281,

[0348] - providing a third pump which is connected at one end to the reservoir 281 and at the other end to a decay line which is connected to a liquid waste device,

[0349] - pumping any excess liquid waste from the reservoir 281 through the decay line and into the liquid waste device by means of the third pump,

[0350] - providing a delivery tube 301 and a second pump 302 to circulate the H 2 15 O saline solution from the reservoir 281 through a loop element 320 and back to the reservoir 281,

[0351] - providing a regulating device 340,

[0352] - Establish the first bolus dose of the H 2 15 O saline solution in the loop element 320, the first bolus dose having a predefined volume and radioactive concentration,

[0353] - Provide a second saline feeder 401,

[0354] - Collect a predefined second bolus dose of saline from the second saline feeder 401,

[0355] - Inject the second bolus dose into the loop element 320 at a predefined rate such that the second bolus dose pushes the first bolus dose into the patient line 520,

[0356] - Measure the injection curve of the first bolus dose with a second radiation detector 440 adjacent to the patient line 520,

[0357] - Adjust the injection curve of the first bolus dose with the injection rate and volume of the second bolus dose.

[0358] 15. The system according to item 8, wherein

[0359] the valve is as described in any one of items 1 to 7, and / or

[0360] the production device is as described in item 9 or 10, and / or

[0361] the bolus dose device is as described in item 11 or 12, and / or

[0362] the adjustment device is as described in item 13, and / or

[0363] the valve is as described in any one of items 1 to 7 and the production device is as described in item 9 or 10, and / or

[0364] the valve is as described in any one of items 1 to 7 and the bolus dose device is as described in item 11 or 12, and / or

[0365] the valve is as described in any one of items 1 to 7 and the adjustment device is as described in item 13, and / or

[0366] the production device is as described in item 9 or 10 and the bolus dose device is as described in item 11 or 12, and / or

[0367] the production device is as described in item 9 or 10 and the adjustment device is as described in item 13, and / or

[0368] The bolus dosage device is as described in item 11 or 12, and the adjustment device is as described in item 13, and / or

[0369] The valve is as described in any one of items 1 to 7, and the production device is as described in item 9 or 10, and the bolus dosage device is as described in item 11 or 12, and / or

[0370] The valve is as described in any one of items 1 to 7, and the production device is as described in item 9 or 10, and the adjustment device is as described in item 13, and / or

[0371] The valve is as described in any one of items 1 to 7, and the bolus dosage device is as described in item 11 or 12, and the adjustment device is as described in item 13, and / or

[0372] The production device is as described in item 9 or 10, and the bolus dosage device is as described in item 11 or 12, and the adjustment device is as described in item 13, and / or

[0373] The valve is as described in any one of items 1 to 7, and the production device is as described in item 9 or 10, and the bolus dosage device is as described in item 11 or 12, and the adjustment device is as described in item 13.

Claims

1. A method for preparing and injecting H 2 15 O for use in positron emission tomography, the method Comprising the following steps: - Convert a gas mixture containing 15 O and H 2 into H 2 15 O, - Providing a valve control element to regulate the flow rate of the gas mixture, - Combine H 2 15 O with the brine from the first brine feeder to produce H 2 15 O brine solution, - Provide a first radiation detector to measure the radioactivity in the 2 15 H O salt solution, - Regulating the flow rate of the gas mixture by means of the first radiation detector, - Provide a reservoir to receive the H 2 15 O salt solution, - Providing a second gas waste device for discharging any excess gas from the reservoir, - Providing a third pump which is connected at one end to the reservoir and at the other end to a decay pipeline, and the decay pipeline is connected to a liquid waste device, - Pumping any excess liquid waste from the reservoir through the decay pipeline and into the liquid waste device by means of the third pump, - Provide a delivery tube and a second pump to circulate the H 2 15 O salt solution from the reservoir through the loop element and back to the reservoir, - Providing a regulating device, - Establish the first bolus of said H 2 15 O saline solution in the loop element, the first bolus having a predefined volume and radioactivity concentration,​​​ - Providing a second saline feeder, - Collecting a pre-defined second bolus volume of saline from the second saline feeder, - Injecting the second bolus volume into the loop element at a pre-defined speed such that the second bolus volume pushes the first bolus volume into the patient pipeline, - Measuring the injection curve of the first bolus volume with a second radiation detector adjacent to the patient pipeline, Thereby regulating the injection curve of the first bolus volume by means of the injection speed and volume of the second bolus volume.

2. An adjustment device for a system for preparing and injecting H 2 15 O used in positron emission tomography, the adjustment device Comprising: - A second saline feeder, - Loop component, the loop component includes the first bolus dose of said H 2 15 O salt solution, - An injection device for collecting a pre - defined second bolus volume of saline from the second saline feeder and injecting the second bolus volume of saline into the loop element at a pre - defined rate such that the second bolus volume of saline pushes the first bolus volume of H 2 15 O saline solution into the patient line, - The loop element is in fluid communication with the patient pipeline, - A second radiation detector adjacent to the patient pipeline, and the radiation detector measures the injection curve of the first bolus volume, - The first brine feeder for providing brine required for preparing H 2 15 O salt solution, Wherein the injection speed and volume of the second bolus volume regulate the injection curve of the first bolus volume.

3. A system for preparing and injecting H 2 15 O for use in positron emission tomography, the system Comprising: - For the production of H 2 15 production device for O salt solution - A bolus dose device for establishing a first bolus dose for injection, the first bolus dose comprising the H 2 15 O saline solution and having a pre-defined volume and radioactivity concentration, the bolus dose device comprising a valve, and - The regulating device for regulating the injection curve of the first bolus volume according to claim 2.

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