Inert gas delivery device, cartridge and trigger system for lung function and structure imaging

Abstract

Delivery devices, cartridges, and triggering systems for lung function and structure imaging using inert gases are provided. An example cartridge (10) configured to be connected to a delivery device (112) for delivering inhalation contrast agent to a patient (124) by inhalation for lung function and structure imaging may include a reservoir (12) containing at least one dose of inhalation contrast agent for delivery to the patient and a closure (14) sealing the at least one dose of inhalation contrast agent in the reservoir. The closure may be configured to open when the cartridge is inserted into the delivery device. A delivery device for delivering an inert gas contrast agent contained in a cartridge to a patient by inhalation for lung function and structure imaging, a lung function and structure imaging system, and a method for imaging a lung of a patient are also provided.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 518,344, filed Aug. 9, 2023, the entire disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure generally relates to delivery devices and systems for delivering diagnostic contrast compositions (“contrast agents”) during diagnostic imaging procedures, and in some non - limiting embodiments, to delivery devices, systems, and related methods for lung imaging that coordinate contrast agent delivery and image scanning during a lung imaging procedure. Background Art

[0004] For example, in the case of pulmonary embolism, COPD (Chronic Obstructive Pulmonary Disease), or IPF (Idiopathic Pulmonary Fibrosis), there is often a medical need to evaluate one or more of the ventilation, air trapping, physical structure, gas exchange, and perfusion status or volume of a patient's lungs or portions thereof. The combination of these medical imaging needs is summarized below as the category of “functional and structural imaging”. In practice, such an evaluation can be accomplished using nuclear medicine imaging techniques, X - ray - based imaging techniques, or magnetic resonance (MR) imaging techniques. Lung evaluations using nuclear medicine imaging techniques can include single - photon emission computed tomography (SPECT) using inhaled SPECT agents and / or blood pool SPECT agents. Lung evaluations using X - ray imaging techniques can include computed tomography (CT) imaging of a patient's lungs while the patient is breathing xenon. When the inhaled xenon dissolves in the patient's blood at the alveoli of the lungs, it can be imaged using CT, for example, to perform functional and structural studies of organs or regions of the body. Lung ventilation can also be evaluated using MR imaging by having the patient breathe a gas containing F - 19 or hyperpolarized xenon. Lung function and structural information can also be evaluated using, for example, gadolinium - based intravenous contrast agents.

[0005] While these existing imaging modalities have many advantages for assessing various lung characteristics, including function, condition, and disease state, they also have many disadvantages. A typical dose of a SPECT imaging agent, such as 50 millicuries (mCi) of rubidium-82 (2E+11 atoms) or 10 mCi of fluorine-18 (3.5E+12 atoms), allows for the collection of dynamic information without additional radiation exposure to the patient. While nuclear medicine-based techniques, including PET and SPECT, have high sensitivity and single-dose radiation exposure, the disadvantages of these techniques are limited spatial resolution and relatively high image noise. A typical CT contrast dose of 100 milliliters containing 370 milligrams of iodine per milliliter corresponds to a dose of 6E+22 molecules and has the advantage of much higher spatial resolution than PET, with a temporal resolution of fractions of a second. However, the disadvantage of CT technology is that an additional radiation dose is required for each image taken. For MR imaging, the MR gadolinium contrast agent dose is typically 10 milliliters at a concentration of 1 millimole (mMol) / milliliter (about 6E+21 atoms of gadolinium). MR has the ability to image hyperpolarized atoms with sensitivity several orders of magnitude higher. For example, an imaging procedure using hyperpolarized xenon gas requires a gas volume on the order of milliliters. However, like radioactivity generated by a cyclotron, hyperpolarization decays spontaneously and requires special and expensive equipment to generate. While MR generally has spatial and temporal resolution between CT and nuclear medicine and has no radiation dose to the patient, gadolinium contrast agents are not easily transferred to the air, and due to the hydrogen atom content relative to surrounding tissues, there are few hydrogen atoms to image, and MR does not receive signals from lung air.

[0006] These modalities can utilize inhaled contrast agents for lung studies. However, traditional inhalation studies are complex and involve the use of complex, expensive, and / or rarely used machines. Therefore, these methods are not used in ordinary clinical practice for assessing ventilation and lung function. Even for pulmonary embolism, where ventilation / perfusion (VQ) SPECT was once the mainstay, CT angiography with intravenous injection of iodinated contrast agents is now the preferred modality. For these reasons, there is a need for convenient and easy-to-use delivery devices, systems, and methods for delivering inhaled contrast agents for lung function and structural imaging, so that inhaled contrast agents for medical imaging can be more widely adopted. Summary of the Invention

[0007] According to non-limiting embodiments, a cartridge is provided that is configured to be connected to a delivery device for delivering an inhaled contrast agent to a patient by inhalation for lung function and structural imaging. The cartridge includes: a reservoir containing at least one dose of the inhaled contrast agent for delivery to the patient; and a closure that seals the at least one dose of the inhaled contrast agent in the reservoir, wherein the closure is configured to open in response to insertion of the cartridge into the delivery device.

[0008] In some non-limiting embodiments, the inhaled contrast agent comprises an inert gas, such as at least one of the following gases: hyperpolarized gas, xenon, krypton, or any combination thereof. In some non-limiting embodiments, the inert gas contains a sufficient amount of atoms with an atomic number higher than 8 to provide enhanced absorption sufficient to increase the Hounsfield unit measurement in the images in a CT imaging system.

[0009] According to a non-limiting embodiment, there is provided a delivery device for delivering a gaseous contrast agent contained in a cartridge. The delivery device includes a reservoir containing at least one dose of the inhaled contrast agent for delivery to a patient by inhalation for pulmonary function and structural imaging. The delivery device includes: a housing defining an interior; a receptacle disposed within the interior of the housing, wherein the receptacle is configured to connect to the cartridge to hold at least a portion of the cartridge within the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with the patient's airway; and at least one valve between the cartridge and the outflow port, wherein when the cartridge is connected to the receptacle, the at least one valve is configured to switch between a first position and a second position. In the first position, the interior of the reservoir of the cartridge is not in fluid communication with the outflow port. In the second position, the interior of the reservoir of the cartridge is in fluid communication with the outflow port so that at least one dose of the inhaled contrast agent can reach the patient's airway through the valve and the outflow port.

[0010] According to a non-limiting embodiment, there is provided a pulmonary function and structural imaging system, including: an imaging device configured to obtain pulmonary function and structural images of a patient; and at least one controller in electronic communication with the imaging device, wherein the at least one controller is configured to: control the delivery device to deliver a dose of the inhaled contrast agent to the patient by inhalation; and control the imaging device to obtain at least one pulmonary function and structural image of the patient, wherein there is inhaled contrast agent in the patient's lungs.

[0011] According to a non-limiting embodiment, there is provided a method for imaging a patient's lungs, including: using a delivery device containing a cartridge to deliver a dose of the inhaled contrast agent to the patient, the cartridge including a reservoir containing at least one dose of the inhaled contrast agent; and after inhaling the dose of the inhaled contrast agent, obtaining at least one pulmonary function and structural image of the patient using the imaging device while the patient holds his or her breath.

[0012] According to non - limiting embodiments, a cartridge is provided that is configured to be connected to a delivery device for delivering an inhaled contrast agent to a patient by inhalation for pulmonary function and structural imaging. The cartridge includes: a reservoir containing at least one dose of inhaled contrast agent for delivery to the patient; and a closure that seals the at least one dose of inhaled contrast agent within the reservoir, wherein the closure is configured to open based on a signal received by the delivery device from a controller.

[0013] In some non - limiting embodiments, the controller is triggered to transmit a signal to the delivery device based on at least one of: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof.

[0014] Aspects of the present disclosure are further characterized by one or more of the following clauses:

[0015] Clause 1. A cartridge configured to be connected to a delivery device for delivering an inhaled contrast agent to a patient by inhalation for pulmonary function and structural imaging, the cartridge including: a reservoir containing at least one dose of inhaled contrast agent for delivery to the patient; and a closure that seals the at least one dose of inhaled contrast agent within the reservoir, wherein the closure is configured to open in response to insertion of the cartridge into the delivery device.

[0016] Clause 2. The cartridge according to Clause 1, wherein the inhaled contrast agent includes an inert gas.

[0017] Clause 3. The cartridge according to Clause 1 or 2, wherein the inert gas includes at least one of: a hyperpolarized gas, xenon, krypton, or any combination thereof.

[0018] Clause 4. The cartridge according to Clause 2 or 3, wherein the inert gas contains a sufficient number of atoms with an atomic number higher than 8 to provide enhanced absorption sufficient to increase the Hounsfield unit measurement in the images in a CT imaging system.

[0019] Clause 5. The cartridge according to any one of Clauses 1 to 4, wherein the reservoir defines a pressurized interior space that contains at least one dose of inhaled contrast agent pressurized to a pressure higher than atmospheric pressure.

[0020] Clause 6. The cartridge according to any one of Clauses 1 to 5, wherein the reservoir contains a single dose of inhaled contrast agent effective for a single pulmonary function and structural imaging procedure.

[0021] Clause 7. The cartridge according to any one of Clauses 1 to 5, wherein the reservoir contains multiple doses of inhaled contrast agent such that the cartridge can be used for multiple pulmonary function and structural imaging procedures.

[0022] Clause 8. The cartridge according to any one of Clauses 1 to 7, wherein the cartridge is a disposable single - use cartridge.

[0023] Clause 9. A cartridge according to any one of Clauses 1 to 7, wherein the cartridge is reusable and recyclable.

[0024] Clause 10. A cartridge according to any one of Clauses 1 to 9, wherein the closure includes a pressure valve that maintains the pressure in the pressurized interior space of the reservoir at a pressure greater than 1.0 atm.

[0025] Clause 11. A delivery device for delivering a contrast agent contained in a cartridge, the delivery device including a reservoir containing at least one dose of an inhaled contrast agent for delivery to a patient by inhalation for pulmonary function and structural imaging, the delivery device including: a housing defining an interior; a socket disposed within the interior of the housing, wherein the socket is configured to connect to the cartridge to hold at least a portion of the cartridge within the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with the patient's airway; and at least one valve between the cartridge and the outflow port, wherein, when the cartridge is connected to the socket, the at least one valve is configured to switch between a first position and a second position, in the first position, the interior of the reservoir of the cartridge is not in fluid communication with the outflow port, and in the second position, the interior of the reservoir of the cartridge is in fluid communication with the outflow port so that at least one dose of the inhaled contrast agent can reach the patient's airway through the valve and the outflow port.

[0026] Clause 12. The delivery device according to Clause 11, further including a mechanical respirator configured to mechanically deliver the inhaled contrast agent from the interior of the reservoir of the cartridge to the patient's airway.

[0027] Clause 13. The delivery device according to Clause 11 or 12, wherein the closure of the cartridge is configured to switch from a closed position to an open position in response to connection of the cartridge to the socket, in the closed position, at least one dose of the inhaled contrast agent is sealed within the interior of the reservoir of the cartridge, and in the open position, at least one dose of the inhaled contrast agent can flow out of the interior of the reservoir of the cartridge.

[0028] Clause 14. The delivery device according to any one of Clauses 11 to 13, wherein the at least one valve is configured such that: when in the first position, at least one of ambient air, oxygen, or any combination thereof reaches the patient's airway through the valve and the outflow port, and when in the second position, at least one of ambient air, oxygen, or any combination thereof does not reach the patient's airway through the valve and the outflow port.

[0029] Clause 15. The delivery device according to Clause 14, wherein the valve is configured to remain in the second position for a predetermined period of time sufficient to deliver one dose of at least one dose of the inhaled contrast agent to the patient, and after the predetermined period of time, automatically return to the first position.

[0030] Clause 16. A pulmonary function and structure imaging system, comprising: an imaging device configured to obtain pulmonary function and structure images of a patient; and at least one controller in electronic communication with the imaging device, wherein the at least one controller is configured to: control a delivery device to deliver an inhalation contrast agent to the patient by inhalation; and control the imaging device to obtain at least one pulmonary function and structure image of the patient, wherein the inhalation contrast agent is in the patient's lungs.

[0031] Clause 17. The pulmonary function and structure imaging system according to Clause 16, wherein the imaging device obtains at least one pulmonary function and structure image during at least one of an inhalation phase, a breath-holding phase, and an exhalation phase.

[0032] Clause 18. The pulmonary function and structure imaging system according to Clause 16 or 17, further comprising a delivery device for delivering an inhalation contrast agent to the patient, the delivery device comprising: a housing defining an interior; a socket disposed within the interior of the housing, wherein the socket is configured to connect to a cartridge to hold at least a portion of the cartridge within the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with the patient's airway; and a valve located between the cartridge and the outflow port, wherein when the cartridge is connected to the socket, at least one valve is configured to transition between a first position and a second position, in the first position, the interior of the reservoir of the cartridge is not in fluid communication with the outflow port, and in the second position, the interior of the reservoir of the cartridge is in fluid communication with the outflow port, such that at least one dose of the inhalation contrast agent can reach the patient's airway through the valve and the outflow port.

[0033] Clause 19. The imaging system according to Clause 18, wherein the delivery device further comprises a mechanical respirator configured to mechanically deliver the inhalation contrast agent from the cartridge to the patient's airway, and wherein the at least one controller is in electrical communication with the mechanical respirator and is configured to actuate the mechanical respirator to mechanically deliver a dose of the inhalation contrast agent from the cartridge to the patient at a predetermined time.

[0034] Clause 20. The imaging system according to any one of Clauses 16 to 19, further comprising at least one of a visual display, an audio output device, or any combination thereof in electrical communication with the at least one controller, wherein the at least one controller is configured to control the visual display, the audio output device, or any combination thereof to provide instructions to the patient to hold his or her breath after inhaling the inhalation contrast agent.

[0035] Clause 21. The imaging system according to Clause 20, wherein the at least one controller is further configured to control the visual display, the audio output device, or any combination thereof to provide instructions to the patient indicating that the patient should inhale a dose of the inhalation contrast agent with the delivery device at a predetermined time.

[0036] Clause 22. A pulmonary function and structural imaging system according to any one of Clauses 18 to 21, wherein the delivery device comprises a handheld manually-operated inhaler.

[0037] Clause 23. An imaging system according to any one of Clauses 16 to 22, further comprising a fluid injector configured to deliver a dose of angiographic contrast agent to a patient's vasculature.

[0038] Clause 24. An imaging system according to Clause 23, wherein at least one controller is configured to control the fluid injector to deliver a dose of angiographic contrast agent to a patient's vasculature and, simultaneously or sequentially, control the delivery device to deliver a dose of inhaled contrast agent to the patient by inhalation.

[0039] Clause 25. An imaging system according to any one of Clauses 16 to 24, wherein the mechanical ventilator comprises at least one sensor, and wherein at least one sensor is configured to monitor a patient's respiration and provide feedback to at least one controller in electronic communication with the imaging device based on the monitored patient respiration.

[0040] Clause 26. A method for imaging a patient's lungs, comprising: delivering a dose of inhaled contrast agent to the patient using a delivery device comprising a cartridge, the cartridge comprising a reservoir containing at least one dose of inhaled contrast agent; and, after inhaling a dose of inhaled contrast agent, obtaining at least one pulmonary function and structural image of the patient while the patient holds his or her breath using an imaging device.

[0041] Clause 27. The method according to Clause 26, wherein delivering a dose of inhaled contrast agent to the patient comprises expelling all or substantially all of the inhaled contrast agent from the reservoir of a single-use cartridge containing a single dose of inhaled contrast agent using the delivery device.

[0042] Clause 28. The method according to Clause 26, wherein delivering a dose of inhaled contrast agent to the patient comprises expelling a single dose of inhaled contrast agent from a reservoir using the delivery device, the reservoir containing multiple doses of inhaled contrast agent.

[0043] Clause 29. The method according to any one of Clauses 26 to 28, further comprising controlling an output device with at least one processor to provide a breath-holding command to the patient after the patient inhales the inhaled contrast agent.

[0044] Clause 30. The method according to any one of Clauses 26 to 29, further comprising injecting an angiographic contrast agent into the patient using a fluid injector and, simultaneously or sequentially, causing the patient to inhale a dose of inhaled contrast agent.

[0045] Clause 31. The method according to any one of Clauses 26 to 30, wherein delivering a dose of an inhalation contrast agent to a patient includes controlling at least one of a visual display, an audio output device, or any combination thereof with at least one processor to provide instructions to the patient to inhale a dose of an inhalation contrast agent from a delivery device, wherein the delivery device is a handheld manually operated inhaler.

[0046] Clause 32. The method according to any one of Clauses 26 to 31, wherein delivering a dose of an inhalation contrast agent to a patient includes mechanically delivering a dose of an inhalation contrast agent to the patient with a mechanical ventilator.

[0047] Clause 33. The method according to Clause 32, wherein delivering a dose of an inhalation contrast agent to a patient includes controlling a valve of the delivery device with at least one processor to move from a first position to a second position to enable a dose of an inhalation contrast agent to flow through the delivery device to the patient, and after a predetermined period of time, returning the valve to the first position to prohibit the inhalation contrast agent from flowing from the delivery device to the patient.

[0048] Clause 34. The method according to Clause 33, wherein when the valve is in the first position, at least one of ambient air, oxygen, or any combination thereof is transmitted through the delivery device to the patient.

[0049] Clause 35. The method according to any one of Clauses 26 to 34, further comprising: monitoring the patient's respiration with at least one sensor; and controlling an output device with at least one processor to provide feedback based on the monitored patient respiration.

[0050] Clause 36. A cartridge configured to be connected to a delivery device for delivering an inhalation contrast agent to a patient by inhalation for pulmonary function and structural imaging, the cartridge comprising: a reservoir containing at least one dose of an inhalation contrast agent for delivery to the patient; and a closure for sealing at least one dose of an inhalation contrast agent in the reservoir, wherein the closure is configured to open based on the delivery device receiving a signal from a controller.

[0051] Clause 37. The cartridge according to Clause 36, wherein the controller is triggered to transmit a signal to the delivery device based on at least one of: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof.

[0052] These and other features and characteristics of the contrast imaging agent, as well as the operating methods and functions of the associated structural elements and component combinations and the manufacturing economy, will become more apparent upon consideration of the following description and the appended claims and reference to the drawings, all of which form a part of this specification, wherein like reference numerals represent corresponding parts in the various figures. Description of the Drawings

[0053] Figure 1Schematic diagram of a cartridge containing an inhaled contrast agent according to a non - limiting embodiment of the present disclosure;

[0054] Figure 2 Schematic diagram of a delivery device for delivering a contrast agent to a patient by inhalation according to a non - limiting embodiment of the present disclosure;

[0055] Figure 3 Schematic diagram of a system for pulmonary function and structural imaging using inhalation of an inert gas contrast agent according to a non - limiting embodiment of the present disclosure; and

[0056] Figure 4 Flowchart showing a method for imaging a patient's lungs according to a non - limiting embodiment of the present disclosure.

[0057] However, it should be clearly understood that the drawings are for illustrative and descriptive purposes only. Detailed Description

[0058] For the purposes of the description hereinafter, the terms "upper", "lower", "right", "left", "vertical", "horizontal", "top", "bottom", "lateral", "longitudinal" and their derivatives shall refer to the components oriented in the drawings. When used in relation to a syringe, the term "proximal" refers to the part of the syringe that is closest to the fluid injector when the syringe is oriented for connection to a fluid injector. The term "distal" refers to the part of the syringe that is furthest from the fluid injector when the syringe and / or the plunger is oriented for connection to a fluid injector. As used in the specification and claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. The term "CT - active amount" refers to the amount of X - ray contrast agent sufficient to obtain X - ray contrast visualization on a CT medical imager. The term "MR - active amount" refers to the amount of MR contrast agent sufficient to obtain visualization on an MR medical imager. The term "air cavity" refers to the passages and gas spaces of alveoli, bronchioles, bronchi, trachea and all other gas - containing structures of the lungs. However, it should be understood that the present disclosure may assume alternative variations and step sequences unless explicitly stated to the contrary. It should also be understood that the specific devices and processes shown in the drawings and described in the following specification are merely exemplary aspects of the present disclosure. Accordingly, specific dimensions and other physical characteristics related to the aspects disclosed herein should not be considered limiting.

[0059] As used herein, the term "computing device" may refer to one or more electronic devices configured to process data. In some examples, a computing device may include the necessary components for receiving, processing, and outputting data, such as a processor, a controller, one or more displays, memory, input devices, a network interface, and the like. A computing device may be a mobile device. As an example, a mobile device may include a cellular phone (e.g., a smart phone or a standard cellular phone), a portable computer (a laptop or a tablet), a wearable device (e.g., a watch, glasses, lenses, clothing, etc.), a personal digital assistant (PDA), and / or other similar devices. A computing device may also be a desktop computer or other forms of non-mobile computers.

[0060] Reference Figures 1 to 4 , non-limiting embodiments of the present disclosure relate to a cartridge 10, a device 110, a system 210, and a method 400 for obtaining a patient lung image for pulmonary function and structural imaging using an inert gas such as xenon (Xe) and / or krypton (Kr), either alone or as a mixture with one or more other gases (e.g., oxygen (O2), air, etc.) as an inhaled diagnostic contrast composition (which may be referred to herein as an "inhaled contrast agent"). For example, an image of a lung containing a dose of the inhalation contrast agent (e.g., an inert gas, etc.) in the pulmonary air cavities can be obtained using a CT medical imager (e.g., a dual-energy CT imager, etc.), an MR medical imager, and the like.

[0061] The inert gas xenon (Xe) is an inert gas with an atomic number (54) close to that of iodine (53), and thus its X-ray absorption characteristics are very similar to those of iodine. In a similar manner, the inert gas krypton (Kr) also exhibits X-ray absorption characteristics. To visualize an inhaled contrast agent such as xenon or krypton on a CT medical imager, the contrast agent should have sufficient contrast with the surrounding tissues to attenuate the X-ray beam from the CT medical imager. For CT imaging, attenuation is measured in Hounsfield units (HU), which defines the radiation density of a material at standard temperature and pressure. Image contrast depends on the voltage of the X-ray tube (in units of kVp). For example, the attenuation of ULTRAVIST ® 370 per mg I / mL dissolved in blood is approximately 19 HU / mgL / ml at 140 kVp and approximately 32 HU / mg I / mL at 90 kVp. The inert gases xenon and krypton will have sufficient X-ray attenuation to provide sufficient image contrast in CT imaging applications. Optionally, hyperpolarization of the gas can allow the inhaled contrast agent to be MRI-active, and the procedures, devices, methods, and embodiments described herein can be used for MR imaging procedures of the pulmonary air cavities.

[0062] Non-limiting embodiments of the present disclosure relate to a container or cartridge 10 containing (multiple) doses of an inhaled contrast agent to be provided to a patient, and a delivery device 110, a system 210, and a method 300 for delivering one or more doses of a (multiple) dose of the inhaled contrast agent from the container or cartridge 10 to the patient by inhalation. For example, the delivery device 110 can be a fully or partially automated electromechanical device (e.g., a ventilator, a respirator, a nebulizer, another mechanical inhalation device, etc.) that delivers a precise dose of an inhaled contrast agent, such as an inert gas, to the patient's airway. In some examples, the cartridge 10 is a disposable, single-use cartridge pre-filled with a single dose of an inhaled contrast agent. Optionally, the cartridge 10 can contain multiple doses of an inhaled contrast agent, and the delivery device 110 can be configured to dispense or release a desired amount of one dose of an inhaled contrast agent at an appropriate time, e.g., for multiple imaging procedures for a single patient, or for providing one dose of an inhaled contrast agent to multiple patients during the course of a day.

[0063] Non-limiting embodiments of the present disclosure relate to a system for pulmonary function and structural imaging using inhalation of an inert gas contrast agent system 210, which is referred to herein as a "trigger system" and is configured to control the delivery device 110 and one or more imaging devices to obtain images of a patient's lungs after inhalation of the inhaled contrast agent. The trigger system 210 can provide instructions or guidance to the patient during an imaging procedure, e.g., by providing breath-holding and / or release instructions or commands at appropriate times during the procedure. The trigger system 210 can be configured to coordinate the operation of other contrast agent injector devices and / or other imaging systems to obtain, for example, dual-energy CT imaging of different body regions, or to control the injection of a vascular imaging contrast agent, e.g., before, after, or simultaneously with the administration of the inhaled contrast agent.

[0064] Figure 1 is a schematic diagram of a cartridge 10 according to a non-limiting embodiment of the present disclosure, the cartridge containing one or more doses of an inhaled contrast agent, the inhaled contrast agent including an inert gas inhaled contrast agent for delivery to a patient for pulmonary function and structural imaging. As used herein, the cartridge 10 can refer to a sealed container configured to be inserted and / or connected to the delivery device 110, e.g., by connection to a socket 116 of the delivery device 112, the socket including means for opening or otherwise accessing the contents of the cartridge 10 and / or for discharging or releasing an inert gas from the cartridge 10 for delivery to the patient.

[0065] As Figure 1As shown, the cartridge 10 includes a container, barrel, or reservoir 12 configured to hold at least one dose of an inhaled contrast agent (e.g., an inert gas, etc.) for delivery to a patient. For example, the reservoir 12 may include a canister defining a pressurized interior sized to hold a single dose or multiple doses of an inhaled contrast agent. The cartridge 10 may include a closure 14 located above an opening 16 of the reservoir 12, and the closure 14 seals the reservoir 12 when the cartridge 10 is not in use (e.g., during shipping, storage, or between uses of the cartridge 10). The closure 14 may be configured to automatically open when the cartridge 10 is inserted into a receptacle 116 of a delivery device 110. As an example, the closure 14 may be configured to transition from a closed position, in which at least one dose of an inhaled contrast agent is sealed within the interior of the reservoir 12 of the cartridge 10, to an open position, in which at least one dose of an inhaled contrast agent can flow out of the interior of the reservoir 12 of the cartridge 10, in response to connection of the cartridge to the receptacle 116 of the delivery device 110. As another example, the closure 14 may be configured to be opened based on receiving a control signal from a system controller 218. For example, the delivery device 110 may be configured to actuate a mechanism (e.g., a cannula, a needle, complementary mating, etc.) for piercing the closure 14 or release the closure 14 from the cartridge 10 in response to a control signal received from the system controller 218. In such an example, the system controller 218 may be triggered to transmit a control signal to the delivery device 110 based on at least one of: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof. Alternatively, the user may manually open or remove the closure 14 immediately before inserting the cartridge 10 into the delivery device 110. In some examples, the closure 14 may be a diaphragm or another barrier that is pierced or removed when the cartridge 10 is inserted into the delivery device 110 or in response to a control signal from the system controller 218. Alternatively or additionally, the closure 14 may include a valve, such as a pressure valve or a check valve, etc., that maintains the pressure within the pressurized interior space of the reservoir 12 at a minimum pressure above atmospheric pressure. For example, the minimum pressure may be 1.5 atm, 5.0 atm, 10.0 atm, or greater, depending on the structure of the cartridge 10, the delivery device 110, and / or the treatment requirements of the imaging procedure being performed. In some examples, the cartridge 10 may include a bag or other container defining a non-pressurized interior sized to hold a single dose or multiple doses of an inhaled contrast agent. For example, the bag may be configured to be compressed or squeezed to deliver the inert gas contained within the reservoir 12, or the bag may be configured to deliver the inert gas contained within the reservoir 12 in response to a negative pressure applied thereto, such as a negative pressure generated by a patient breathing through the delivery device 110 when the cartridge 10 is connected to the delivery device 110.

[0066] The cartridge 10 can be configured to contain any gas suitable for use as an inhaled contrast agent in pulmonary function and structural imaging. For example, as previously described, the gas can be an inert gas such as xenon, krypton, or a combination thereof. For example, since krypton has a lower opacity to x-rays than xenon, krypton can be used at a higher concentration compared to the concentration of xenon. In some examples, the gas can be a hyperpolarized gas. In some examples, the inert gas includes a sufficient amount of atoms with an atomic number higher than 8 to provide enhanced absorption sufficient to increase the Hounsfield unit measurement in the image in a CT imaging system. In some examples, the gas can include a mixture of oxygen and a noble gas such as xenon, krypton, or a combination thereof. In other examples, the gas can include a mixture of air and a noble gas such as xenon, krypton, or a combination thereof. Examples of injectable gas contrast agents, which include noble gases or other gases with x-ray opacity and which can be used with the cartridges, delivery devices, and systems disclosed herein, are described in detail in U.S. Patent No. 11,576,985, the entire content of which is incorporated herein by reference in its entirety.

[0067] According to certain embodiments, the cartridge 10 can be a disposable, single-use cartridge 10 that contains a single dose of inhaled contrast agent to be delivered to a patient. In other examples, the cartridge 10 can be a reusable, refillable, and / or recyclable cartridge that contains a multi-dose of inhaled contrast agent for use during multiple pulmonary function and structural imaging procedures. As used herein, a single dose of noble gas refers to an effective amount of noble gas to obtain a suitable quality of pulmonary function and structural images according to the imaging technique being performed. For example, for x-ray imaging, the dose of inert gas in the reservoir 12 can be a CT-effective amount, meaning the amount of inhaled contrast agent sufficient to provide proper visualization of x-ray contrast on a CT medical imager. In a similar manner, for MR imaging, the dose of inhaled contrast agent in the reservoir 12 can be an MR-effective amount of gas, meaning the amount of MR contrast agent sufficient to provide visualization on an MR medical imager.

[0068] Figure 2FIG. 0 is a schematic view showing an embodiment of a delivery device 110 that receives a cartridge 10 and controls the release of an inhalation contrast agent, such as an inert gas, contained in the cartridge 10 for delivering one or more doses of the contrast agent to a patient 124. For example, the cartridge 10 may be a removable and / or replaceable cartridge 10 that is inserted into the delivery device 110 prior to an imaging procedure and, in the case of a single-dose cartridge 10, removed after completion of the imaging procedure of the patient's 124 lung function and structure, or in the case of a multi-dose cartridge, when the reservoir 12 of the cartridge 10 is empty. In some embodiments, inserting the cartridge 10 into the delivery device 110 may cause the closure 14 of the cartridge 10 to automatically open or rupture, i.e., move to a second position. For example, the delivery device 110 may include a mechanism (e.g., cannula, needle, complementary fit, etc.) for piercing the closure 14 or releasing the closure 14 from the cartridge 10 to access the inert gas contained in the reservoir 12.

[0069] As Figure 2 shown, the drug delivery device 110 includes a housing 112 that defines an interior sized to receive at least a portion of the cartridge 10. For example, the housing 112 may be a cylindrical, box-shaped, or other shaped enclosure that includes a port or opening 114 configured to insert the cartridge 10 into the housing 112. The delivery device 110 may include a socket 116 disposed inside the housing 112, e.g., at the distal end of the opening 114, that holds at least a portion of the cartridge 10 and closure 14 within the housing 112. For example, the socket 116 may be configured to connect to the cartridge to hold at least a portion of the cartridge within the housing 112. For example, the socket 116 and / or the cartridge 10 may include locking features (e.g., Luer lock mechanism, bayonet lock mechanism, screw lock mechanism, etc.) for connecting the cartridge 10 to the socket 116 of the delivery device 110, and a mechanism (e.g., cannula, needle, complementary fit, etc.) for opening the closure 14 or accessing the gas contents of the cartridge 10 and for discharging the inert gas contained therein from the reservoir 12 to the patient 124.

[0070] The delivery device 110 may also include an outflow port 118 connected to a delivery feature (patient attachment 126), a delivery component such as a mouthpiece, breathing mask, nozzle, and / or the like, that extends through the housing 112, which is configured to be positioned in fluid communication with the airway of the patient 124. In some examples, the patient 124 may place a mouthpiece, breathing mask, or nozzle in their mouth for delivering a dose of the inhalation contrast agent directly into the patient's airway. In other examples, a dose of the inhalation contrast agent may be delivered to the patient's airway through the patient attachment 126 (e.g., mask, nasal cannula, breathing tube, or similar device) that is connected to the outflow port 118 of the delivery device 110 via, for example, a flexible tubing 128.

[0071] The delivery device 110 may also include a valve 120 between the socket 116 (and the cartridge 10) and the outflow port 118. For example, the socket 116 may be configured to place the cartridge 10 (e.g., the interior of the reservoir 12 of the cartridge 10, etc.) in fluid communication with the valve 120 when the cartridge 10 is connected to or engaged with the socket 116. As an example, the valve 120 may be configured to transition between a first position and a second position, in the first position, the interior of the reservoir 12 of the cartridge 10 is not in fluid communication with the outflow port 118, and in the second position, the interior of the reservoir 12 of the cartridge 10 is in fluid communication with the outflow port 118, such that at least one dose of the inhaled contrast agent can reach the patient's airway through the valve 120 and the outflow port 118. For example, the valve 120 may be configured to transition between a first position or a closed position and a second position or an open position, in the first position or the closed position, a dose (or multiple doses) of the inhaled contrast agent is sealed in the reservoir 12 of the cartridge 10, and in the second position or the open position, a dose (or multiple doses) of the inhaled contrast agent reaches the airway of the patient 124 through the valve 120 and the outflow port 118. In some examples, the valve 120 may be configured to transition between providing ambient air (e.g., indoor, atmospheric, etc.) or oxygen to the patient 124 and providing the inhaled contrast agent from the cartridge 10 to the patient 124. For example, as Figure 2 shown, the valve 120 may be configured such that when in the closed position, ambient air or oxygen reaches the airway of the patient 124 through the valve 120 and the outflow port 118, as Figure 2 shown by arrow A1 in. When the valve 120 is in the open position, ambient air or oxygen may be prevented from passing through the valve 120 and the outflow port 118. Instead, when the valve 120 is in the open position, as Figure 2 shown by arrow A2 in, the inhaled contrast agent reaches the patient's airway from the cartridge 10 through the valve 120 and the outflow port 118. In some examples, the valve 120 may be configured to remain in the open position for only a predetermined period of time, after which the valve 120 automatically closes. For example, the valve 120 may be configured to open for a predetermined period of time that is sufficient to deliver a single dose of the contrast agent to the patient 124, and after the predetermined time, it may automatically return to the closed position. In certain embodiments, the valve 120 may provide a mixture of ambient air / oxygen and the inhaled contrast agent, for example to control the concentration of the inhaled contrast agent dose. As previously described, when the valve 120 is in the closed position, ambient air or oxygen may be delivered to the patient 124 through the outflow port 118 or the mouthpiece.

[0072] In some embodiments, valve 120 may include a two-way valve. For example, a first input of valve 120 may be connected to receptacle 116, and a second input of valve 120 may be connected to an ambient air or oxygen source. In some implementations, valve 120 may include a three-way valve. For example, a first input of valve 120 may be connected to receptacle 116, a second input of valve 120 may be connected to ambient air, and a third input of the valve may be connected to an oxygen source. In such an example, system controller 218 may be configured to control delivery device 110 to control valve 120 to switch between connecting one or more of the inputs to outflow port 218 in accordance with user input and / or an inhalation contrast agent delivery protocol.

[0073] Delivery device 110 may be a manually activated device or an automated device. For example, delivery device 110 may be a handheld or portable inhaler that may be activated when a user (e.g., patient 124) presses a release button or similar mechanism to open valve 120. The release button may also activate, for example, a piston, plunger, or similar compression mechanism for ejecting a dose of inhalation contrast agent from reservoir 12 of cartridge 10. Optionally, the inhalation contrast agent may be pressurized within cartridge 10 at a pressure greater than atmospheric pressure such that upon activation, due to the release of pressure, the inhalation contrast agent flows towards the patient.

[0074] Continuing to refer Figure 2 to, delivery device 110 may include an automated device such as a respirator 122, ventilator, inhaler, nebulizer, or similar inhalation device including a pump for mechanical delivery of a breath with a dose (multiple doses) of inhalation contrast agent or for pressure release of pressurized inhalation contrast agent into the airway of patient 124. Upon activation of respirator 122 or a similar device, the dose of contrast agent may be withdrawn from reservoir 12 of cartridge 10 and delivered to the patient by one or more mechanical breaths.

[0075] Figure 3 is a schematic illustration of a pulmonary function and structural imaging system 210 according to a non-limiting embodiment of the present disclosure that may be used with cartridge 10 and delivery device 110 of the present disclosure. As previously described, system 210 may be configured to coordinate the release of inhalation contrast agent from delivery device 110 for inhalation by patient 124, image scanning of the (multiple) lungs of the patient using one or more imaging devices, and any other imaging techniques or procedures that may be performed on the patient simultaneously or sequentially with the pulmonary function and structural imaging process. As previously described, the images captured by system 210 may be used to evaluate one or more of ventilation, air trapping, physical structure, gas exchange, perfusion status, or volume of the lungs or lung portions of the patient.

[0076] As Figure 3As shown, the system 210 may include an imaging device 212 configured to obtain pulmonary function and structural images of a patient 124. For example, the imaging device 212 may be a CT medical imager used in conjunction with X-ray contrast and / or an MR imager using, for example, hyperpolarized inert gas. An exemplary imaging device 212 is described in U.S. Patent Application Publication No. 2022 / 0401588 (Flohr et al.), which can be used to acquire images of various contrast agents and / or different functional regions of a patient's body and can be used in conjunction with the system 210 and method 300 disclosed herein, and this patent application is incorporated herein by reference in its entirety. The system 210 may also include a delivery device 110 for delivering a contrast agent from a cartridge 10 containing an appropriate contrast agent to the patient 124 by inhalation. As previously described, the delivery device 110 may be a manual device, such as a handheld inhaler, or an automated delivery device, such as a respirator 122 or a ventilator.

[0077] In some examples, the system 210 may also include one or more computer input and output devices for receiving information from a system user or the patient 124 and for providing instructions, information, and / or feedback to the user and / or the patient. For example, the system 210 may include an input device 214, such as a terminal, a user interface, a keyboard, or a touchscreen display, and / or the like that enables a user to input information about the patient 124 and / or the program being performed. The system 210 may include an output component, such as a visual display 216, an audio output component, etc., for providing information and instructions to the system user and / or the patient 124.

[0078] Continuing to refer Figure 3 to, the system 210 further includes a controller 218, such as a computing device or a computer processor, which is in electrical communication with one or more of the imaging device 212, the delivery device 110, and / or other system 210 components. The controller 218 may be configured to coordinate the delivery of the inhaled contrast agent, the angiographic contrast agent, and / or the image scan to obtain pulmonary function and structural images. For example, the controller 218 may be configured to administer a dose of the inhaled contrast agent from the delivery device 110 to the patient 124. The controller 214 may be configured to cause the imaging device 212 to obtain pulmonary function and structural images of the patient with the inhaled contrast agent in the patient's lungs after the patient 124 inhales a dose of the inhaled contrast agent. In certain procedures, the controller 214 may also be configured to control or manage the injection of the angiographic contrast agent from a fluid injector 220, as described herein.

[0079] In some examples, imaging of the lungs of patient 124 may be performed during at least one of the following periods: an inspiration period (e.g., the time period during which patient 124 inhales a dose of inhaled contrast agent into their lungs), a breath-hold period (e.g., the time period during which patient 124 holds a dose of inhaled contrast agent in their lungs without inhaling or exhaling), an expiration period (e.g., the time period during which patient 124 exhales a dose of inhaled contrast agent from their lungs), a time period prior to the inspiration period or after the expiration period (e.g., when patient 124 is in imaging device 212 but has no inhaled contrast agent in their lungs), or any combination thereof. Additionally, in some examples, controller 218 may be configured to cause imaging device 212 to obtain or capture a series of lung images. For example, controller 218 may be configured to cause imaging device 212 to obtain multiple images at different times according to, for example, a pulmonary function and structure imaging protocol. For example, in an exemplary imaging protocol, controller 218 may be configured to cause imaging device 212 to obtain a first image of the lungs immediately or shortly (e.g., within 1 second to 10 seconds) after patient 124 inhales the inhaled contrast agent, and a second or delayed image of the lungs after a breath-hold period at other predetermined delay times (e.g., 30 seconds, 1 minute, 5 minutes, or longer delays) to show the change in contrast agent concentration in the pulmonary air cavities over time.

[0080] When delivery device 110 is an automated or mechanical delivery device, such as respirator 122 or ventilator, controller 218 may be configured to control delivery device 110 such that a dose of inhaled contrast agent is delivered at an appropriate time prior to obtaining the lung images. For example, controller 218 may be configured to actuate delivery device 110 and cause imaging device 212 to obtain functional and structural images during a breath-hold period, for example, a predetermined time period (e.g., 1 second, 2 seconds, 5 seconds, 10 seconds, or longer) after the patient inhales the contrast agent. Controller 218 may be configured to provide instructions to the patient on a visual display 216 or an audible output indicating when the patient should breathe and / or hold his or her breath when the inhaled contrast agent is provided. For example, instructions for patient 124 to hold their breath after inhaling the contrast agent may be displayed on visual display 216 such that the contrast agent remains in the patient's lungs for at least a predetermined time period.

[0081] When the delivery device 110 is a manually activated or controlled device (e.g., a handheld or portable inhaler, etc.), instructions on when to use the inhaler can be displayed or announced on, for example, the visual display 216 or the auditory output device of the system 210. For example, the controller 218 can be configured to cause instructions such as "inhale now" or "take a deep breath" to be displayed on the visual display 216 to notify the patient 124 when to use the inhaler device 110. Instructions on having the patient hold their breath after inhaling the inhalation contrast agent can also be displayed on the visual display 216. As in the previous example, the controller 214 can be configured to cause the imaging device 212 to obtain functional and structural images of the patient's lungs at a predetermined time period (e.g., 1 second, 2 seconds, 5 seconds, 10 seconds or longer) after the instruction to display the inhalation contrast agent is given.

[0082] Continuing to refer Figure 3 , the system 210 can also include another delivery device, such as a manually operated or powered fluid injector 220, for delivering another diagnostic angiographic contrast agent (referred to herein as "angiographic contrast agent") into, for example, the bloodstream of a patient. For example, the fluid injector 220 can be configured to deliver an effective amount of the angiographic contrast agent (e.g., a CT imaging contrast agent, an MR imaging contrast agent, tungsten, etc.) from a container or syringe mounted to the fluid injector 220 through a disposable kit or catheter assembly into the vasculature of the patient 124. Exemplary syringes and powered fluid injectors suitable for use as the powered fluid injector 220 are described, for example, in U.S. Patent No. 5,383,858, U.S. Patent No. 7,553,294, U.S. Patent No. 7,666,169, U.S. Patent No. 8,945,051, U.S. Patent No. 9,173,955, U.S. Patent No. 9,199,033, U.S. Patent No. 10,022,493, and U.S. Patent No. 10,507,319, International Patent Application No. PCT / US2012 / 037491, and U.S. Application Publication No. 2014 / 0027009, the disclosures of which are incorporated herein by reference in their entirety.

[0083] In some examples, the fluid injector 220 for the angiographic agent can be a multi-syringe injector, where two or more syringes can be oriented side-by-side or in other arrangements and include plungers actuated individually by respective pistons associated with the injection. The fluid injector 220 can be configured to receive a syringe filled with the angiographic agent and one or more additional syringes filled with different fluids (such as saline or another angiographic agent), and the fluid injector 220 can be used to deliver saline and / or the (multiple) angiographic compositions into the patient 124. The fluid delivery from the multiple syringes can be controlled by the fluid injector 220 and / or the controller 218. The fluid flow from the syringes can be regulated by a fluid control module (not shown) of the fluid injector 220. The fluid control module can operate various pistons, valves, and / or flow regulation structures of the fluid injector 220 to regulate the delivery of the medical fluid, such as saline solution and angiographic agent, to the patient 124 based on user-selected injection parameters, such as injection flow rate, duration, total injection volume, and / or the ratio of the contrast agent and saline. Other examples of related multi-fluid delivery systems that can be modified for use with the present system 210 are described in U.S. Patent No. 7,553,294, U.S. Patent No. 7,666,169, U.S. Patent No. 9,474,857, and International Patent Application Publication No. WO2012 / 155035, the disclosures of which are incorporated herein by reference.

[0084] In addition to the other components of the pulmonary function and structure imaging system 210, the controller 218 can also be in electrical communication with the fluid injector 220 and can be configured to coordinate the fluid delivery of the fluid injector 220 and the delivery of the inhaled contrast agent of the delivery device 110. For example, the controller 218 can be configured to cause the fluid injector 220 to deliver an effective amount of the angiographic agent to the vasculature of the patient 124 before, at the same time as, substantially simultaneously with (such as within 1 second to 5 seconds, etc.), or after the administration of an effective dose of the inhaled contrast agent from the delivery device 110 to the lungs of the patient 124 by inhalation. As an example, the controller 218 can control the fluid delivery of the fluid injector 220 to be earlier than the delivery of the inhaled contrast agent (such as 15 minutes earlier, 30 minutes earlier), such that the imaging device 212 can obtain functional and structural images showing each of the inhaled contrast agent in the lungs of the patient 124 and the angiographic agent in the vasculature in a single scan, where the lungs are filled with the inhaled contrast agent and the angiographic agent is fully in the patient's blood. In another example, for the simultaneous administration of the angiographic agent from the fluid injector 220 and the inhaled contrast agent from the delivery device 110, the controller 218 can be configured such that the imaging device 212 obtains functional and structural images that show each of the contrast agent inhaled into the lungs and the angiographic agent in the vasculature of the patient 124, such as when the angiographic agent is throughout the vasculature of the patient 124.

[0085] The cartridge 10, delivery device 110, and trigger system 210 disclosed herein can be used in a method for imaging the lungs of a patient 124. Generally, for a diagnostic imaging procedure, the patient 124 is placed on an imaging platform and typically remains supine, lateral, or prone during the imaging procedure. However, for some lung imaging, it may be desirable for the patient to be in an upright position.

[0086] Now referring to Figure 4 , a flowchart of a method 400 for imaging the lungs of a patient in accordance with a non-limiting embodiment of the present disclosure is shown. Figure 4 The steps shown in

[0087] are for illustrative purposes only. It will be understood that in some non-limiting embodiments or aspects, additional, fewer, different, and / or different-order steps may be used. In some non-limiting embodiments, steps may be automatically performed in response to the execution and / or completion of a previous step. Figure 4 As shown in

[0088] , at step 402, method 400 includes delivering a dose of inhaled contrast agent to patient 124 using delivery device 110. For example, delivery device 110 that includes cartridge 10 can deliver a dose of inhaled contrast agent to patient 124, where cartridge 10 includes a reservoir 12 containing at least one dose of inhaled contrast agent. For example, patient 124 can be instructed to inhale a dose of inhaled contrast agent using delivery device 110 as described herein. As previously described, the inhaled contrast agent can be contained in a removable and / or replaceable cartridge 10 inserted into delivery device 110 (e.g., a single-use pre-filled cartridge containing a single dose of inhaled contrast agent, a multi-use cartridge containing multiple doses of contrast agent, etc.). For a single-use cartridge, method 400 can include expelling all or substantially all (e.g., a predetermined percentage, etc.) of the inert gas from reservoir 12 of cartridge 10 to patient 124. For a cartridge 10 containing multiple doses of inhaled contrast agent, method 400 can include controlling valve 120, breather 122, closure 14, and / or similar components of delivery device 110 or cartridge 10 such that a desired amount (e.g., a single dose or each dose of the multiple doses) of inhaled contrast agent is expelled from reservoir 12 of cartridge 10 at an appropriate time.The delivery device 110 can be an automated delivery device (e.g., a respirator 122, a ventilator, etc.) or a manual delivery device (e.g., a handheld inhaler, etc.) as described herein. For an automated delivery device, delivering a dose of inhaled contrast agent can include actuating the respirator 122 and moving the valve 120 to an open position such that the inhaled contrast agent flows from the reservoir 12 of the cartridge 10 to the patient 124. In some examples, as previously described, the valve 120 can be configured to automatically close after a predetermined period of time to ensure that the correct amount of inhaled contrast agent is delivered to the patient 124. For a manual delivery device, delivering a dose of inhaled contrast agent can include instructing the patient to use the inhaler and / or assisting the patient in using the inhaler at the appropriate time.

[0089] As Figure 4 shown, at step 404, method 400 includes providing an instruction to the patient to hold his or her breath. For example, the system controller 218 can control the visual display 216 and / or the auditory output device to provide an instruction to the patient to hold his or her breath. As an example, after the patient 124 inhales the inhaled contrast agent, the system controller 218 can receive an indication that a dose of inhaled contrast agent has been delivered from the delivery device 110, and in response to receiving the indication that the inhaled contrast agent has been delivered, provide an instruction to the patient to hold his or her breath such that the inhaled contrast agent remains in the air cavities of the patient's lungs. For example, as previously described, the breath-holding instruction or command can be displayed on the visual display 216 or emitted from the auditory output device of the system 210.

[0090] As Figure 4 shown, at step 406, method 400 includes optionally injecting a contrast agent into the patient's vasculature, such as in an imaging procedure that combines the administration of the inhaled contrast agent and the injection of the contrast agent. For example, the fluid injector 220 (e.g., in response to a command from the system controller 218, in response to user input, etc.) can inject the contrast agent into the vasculature of the patient 124 before, at the same time as, or substantially simultaneously with and / or after delivering a dose of inhaled contrast agent to the patient 124. For example, the contrast agent can be injected by actuating the fluid injector 220 such that the contrast agent enters the patient's bloodstream from the fluid injector 220 through a catheter kit or assembly.

[0091] As Figure 4As shown, at step 408, method 400 includes obtaining pulmonary function and structural images of a patient. For example, imaging device 212 can obtain pulmonary function and structural images of patient 124. As an example, after inhaling a dose of inhalation contrast agent and optionally injecting an angiographic contrast agent, and with patient 124 holding his or her breath, imaging device 212 can be used to obtain pulmonary function and structural images of patient 124. Images can be obtained before, simultaneously or substantially simultaneously with, and / or after the delivery of a dose of inhalation contrast agent, or after a predetermined delay (e.g., a delay of 5 seconds to 15 seconds, etc.). In some examples, imaging device 212 can be used to collect one or more consecutive images while patient 124 holds his / her breath, showing how the inhalation contrast agent evolves into the lungs over time. For example, at the end of the breath-holding phase, e.g., after 5 seconds to 15 seconds, imaging device 212 can continue to collect images while patient 124 takes one or more breaths, showing how the inhalation contrast agent flushes out of the lungs. In certain embodiments, the method can include obtaining a second consecutive set of pulmonary function and structural images after a predetermined period of time (e.g., from 1 minute to 30 minutes) after obtaining an initial set of pulmonary function and structural images, to visualize the amount of contrast agent in the air cavities of the lungs after the predetermined period of time.

[0092] In some examples, method 400 includes obtaining multiple images of a patient's lungs according to a predetermined imaging protocol. In some examples, the imaging protocol can include taking images during each of an inhalation phase, a breath-holding phase (e.g., when the patient holds their breath with contrast agent in their lungs), and an exhalation phase (e.g., when the inhaled contrast agent flows out of the lungs). For example, the imaging protocol can include taking one or more images of the patient's lungs during the inhalation phase. The imaging protocol can include taking one or more images during the breath-holding phase, e.g., a breath-holding phase that lasts from about 5 seconds to about 30 seconds after inhaling the contrast agent. The imaging protocol can include taking one or more images during the exhalation phase when patient 124 exhales. Images can be taken after a predetermined period of time and / or at a predetermined constant or variable interval (e.g., 2 seconds, 5 seconds, 10 seconds to about 30 seconds, with a total time of about 5 minutes after the breath-holding phase) to allow the gas to wash out of the patient's lungs substantially completely. In some examples, the method can further include performing one or more high-dose, high-resolution scans and one or more low-dose, low-resolution scans on the dynamic data. Image acquisition and analysis can be similar to those performed in, for example, PET and SPECT.

[0093] As described above, the imaging device 212 can include a CT medical imager and / or an MR imager, depending on the type of inhalation contrast agent used. In addition, when the contrast agent is provided to each air cavity of the lungs and the patient's vasculature, the imaging device 212 can be configured to detect or visualize each contrast agent. For example, the imaging device 212 can be a dual-energy CT imager configured to obtain images that visualize each of the inert gas in the lungs and the angiographic agent in the patient's bloodstream.

[0094] Although the present disclosure has been described in detail for purposes of illustration based on presently considered to be the most practical and preferred aspects, it is to be understood that such detail is solely for that purpose and that the present disclosure is not limited to the disclosed aspects, but on the contrary, is intended to cover modifications and equivalent arrangements. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any aspect can be combined with one or more features of any other aspect.

Claims

1. A cartridge configured to be connected to a delivery device for delivering an inhaled contrast agent to a patient by inhalation for pulmonary function and structural imaging, the cartridge comprising: a reservoir containing at least one dose of the inhaled contrast agent for delivery to the patient; and a closure for sealing the at least one dose of the inhaled contrast agent in the reservoir, wherein the closure is configured to open in response to insertion of the cartridge into the delivery device.

2. The cartridge according to claim 1, wherein, The inhaled contrast agent comprises an inert gas.

3. The cartridge according to claim 2, wherein, The inert gas comprises at least one of a hyperpolarized gas, xenon, krypton, or any combination thereof.

4. The cartridge according to claim 2 or 3, wherein, The inert gas contains a sufficient number of atoms having an atomic number higher than 8 to provide enhanced absorption sufficient to increase the Hounsfield unit measurement in an image in a CT imaging system.

5. The cartridge according to any one of claims 1 to 4, wherein, The reservoir defines a pressurized interior space containing the at least one dose of the inhaled contrast agent pressurized to a pressure higher than atmospheric pressure.

6. The cartridge according to any one of claims 1 to 5, wherein, The reservoir contains a single dose of the inhaled contrast agent effective for a single pulmonary function and structural imaging procedure.

7. The cartridge according to any one of claims 1 to 5, wherein, The reservoir contains multiple doses of the inhaled contrast agent such that the cartridge can be used for multiple pulmonary function and structural imaging procedures.

8. The cartridge according to any one of claims 1 to 7, wherein The cartridge is a disposable single-use cartridge.

9. The cartridge according to any one of claims 1 to 7, wherein, The cartridge is reusable and recyclable.

10. The cartridge according to any one of claims 1 to 9, wherein, The closure includes a pressure valve that maintains the pressure within the pressurized interior space of the reservoir at a pressure greater than 1.0 atm.

11. A delivery device for delivering a contrast agent contained in a cartridge, the delivery device including a reservoir containing at least one dose of an inhaled contrast agent for delivery to a patient by inhalation for pulmonary function and structural imaging, the delivery device comprising: a housing defining an interior; a socket disposed within the interior of the housing, wherein the socket is configured to connect to the cartridge to hold at least a portion of the cartridge within the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with the patient's airway; and at least one valve between the cartridge and the outflow port, wherein when the cartridge is connected to the socket, the at least one valve is configured to transition between a first position and a second position, in the first position, the interior of the reservoir of the cartridge is not in fluid communication with the outflow port, and in the second position, the interior of the reservoir of the cartridge is in fluid communication with the outflow port to enable the at least one dose of the inhaled contrast agent to reach the patient's airway through the valve and the outflow port.

12. The delivery device according to claim 11, further comprising a mechanical respirator configured to mechanically deliver the inhaled contrast agent from the interior of the reservoir of the cartridge to the patient's airway.

13. The delivery device according to claim 11 or 12, wherein, The closure of the cartridge is configured to transition from a closed position, in which at least one dose of the inhaled contrast agent is sealed inside the reservoir of the cartridge, to an open position in response to connection of the cartridge to the receptacle, in which open position the at least one dose of the inhaled contrast agent can flow out from inside the reservoir of the cartridge.

14. The delivery device according to any one of claims 11 to 13, wherein, The at least one valve is configured such that when in the first position, at least one of ambient air, oxygen, or any combination thereof passes through the valve and the outflow port to the airway of the patient, and when in the second position, at least one of the ambient air, the oxygen, or any combination thereof does not pass through the valve and the outflow port to the airway of the patient.

15. The delivery device according to claim 14, wherein, The valve is configured to remain in the second position for a predetermined period of time sufficient to deliver one dose of the at least one dose of the inhaled contrast agent to the patient and, after the predetermined period of time, automatically return to the first position.

16. A pulmonary function and structure imaging system, comprising: an imaging device configured to obtain pulmonary function and structure images of a patient; and at least one controller in electronic communication with the imaging device, wherein the at least one controller is configured to: control a delivery device to deliver a dose of an inhaled contrast agent to the patient by inhalation; and control the imaging device to obtain at least one pulmonary function and structure image of the patient in which the inhaled contrast agent is present in the lungs of the patient.

17. The imaging system according to claim 16, wherein The imaging device obtains the at least one pulmonary function and structure image during at least one of an inspiration phase, a breath-hold phase, and an expiration phase.

18. The imaging system according to claim 16 or 17, further comprising a delivery device for delivering the dose of the inhaled contrast agent to the patient, the delivery device comprising: a housing defining an interior; a receptacle disposed inside the housing, wherein the receptacle is configured to connect to a cartridge to hold at least a portion of the cartridge inside the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with the airway of the patient; and a valve located between the receptacle and the outflow port, wherein when the cartridge is connected to the receptacle, the at least one valve is configured to transition between a first position and a second position, in the first position, the interior of the reservoir of the cartridge is not in fluid communication with the outflow port, and in the second position, the interior of the reservoir of the cartridge is in fluid communication with the outflow port such that at least one dose of the inhaled contrast agent can reach the airway of the patient through the valve and the outflow port.

19. The imaging system according to claim 18, wherein, The delivery device further comprises a mechanical ventilator configured to mechanically deliver the inhaled contrast agent from the cartridge to the airway of the patient, and wherein the at least one controller is in electrical communication with the mechanical ventilator and is configured to actuate the mechanical ventilator to deliver the dose of the inhaled contrast agent from the cartridge to the patient at a predetermined time.

20. The imaging system according to any one of claims 16 to 19, further comprising at least one of a visual display, an audio output device, or any combination thereof, in electrical communication with the at least one controller, Among them, wherein the at least one controller is configured to control at least one of the visual display, the audio output device, or any combination thereof to provide an instruction to the patient to hold his or her breath after the patient inhales the inhalation contrast agent.

21. The imaging system according to claim 20, wherein, The at least one controller is further configured to control at least one of the visual display, the audio output device, or any combination thereof to provide an instruction to the patient indicating that the patient should inhale the dose of inhalation contrast agent with the delivery device at a predetermined time.

22. The imaging system according to any one of claims 18 to 21, wherein The delivery device includes a handheld manually operated inhaler.

23. The imaging system according to any one of claims 16 to 22, further comprising a fluid injector configured to deliver a dose of angiographic contrast agent to the patient's vasculature.

24. The imaging system according to claim 23, wherein, The at least one controller is configured to control the fluid injector to deliver the dose of angiographic contrast agent to the patient's vasculature and, simultaneously or sequentially, control the delivery device to deliver the dose of inhalation contrast agent to the patient by inhalation.

25. The imaging system according to any one of claims 16 to 24, wherein, The mechanical ventilator includes at least one sensor, wherein the at least one sensor is configured to monitor the patient's breathing and provide feedback to the at least one controller in electronic communication with the imaging device based on the monitored patient breathing.

26. A method for imaging a patient's lungs, comprising: delivering a dose of inhalation contrast agent to a patient using a delivery device comprising a cartridge, the cartridge including a reservoir containing at least one dose of inhalation contrast agent; and obtaining at least one image of the patient's lung function and structure using an imaging device while the patient holds his or her breath after inhaling the dose of inhalation contrast agent.

27. The method according to claim 26, wherein, Delivering the dose of inhalation contrast agent to the patient includes expelling all or substantially all of the inhalation contrast agent from the reservoir of a single-use cartridge containing a single dose of the inhalation contrast agent using the delivery device.

28. The method according to claim 26, wherein, Delivering the dose of inhalation contrast agent to the patient includes expelling a single dose of the inhalation contrast agent from the reservoir using the delivery device, wherein the reservoir contains multiple doses of the inhalation contrast agent.

29. The method according to any one of claims 26 to 28, further comprising controlling an output device with at least one processor to provide a breath-holding command to the patient after the patient inhales the inhalation contrast agent.

30. The method according to any one of claims 26 to 29, further comprising injecting an angiographic contrast agent into the patient using a fluid injector and delivering the dose of inhalation contrast agent to the patient simultaneously or sequentially.

31. The method according to any one of claims 26 to 30, wherein Delivering the dose of inhalation contrast agent to the patient further includes controlling at least one of a visual display, an audio output device, or any combination thereof with at least one processor to provide an instruction to the patient to inhale the dose of inhalation contrast agent from the delivery device, wherein the delivery device is a handheld manually operated inhaler.

32. The method according to any one of claims 26 to 31, wherein, Delivering the dose of inhalation contrast agent to the patient includes delivering the dose of inhalation contrast agent to the patient with a mechanical ventilator.

33. The method according to claim 32, wherein, Delivering the dose of inhalation contrast agent to the patient includes controlling, with at least one processor, a valve of the delivery device to move from a first position to a second position to enable the dose of inhalation contrast agent to flow through the delivery device to the patient, and after a predetermined time period, returning the valve to the first position to prohibit the inhalation contrast agent from flowing from the delivery device to the patient.

34. The method according to claim 33, wherein When the valve is in the first position, the method includes causing at least one of ambient air, oxygen, or any combination thereof to flow through the delivery device to the patient.

35. The method according to any one of claims 26 to 35, further comprising: monitoring the patient's respiration with at least one sensor; and controlling an output device with at least one processor to provide feedback based on the monitored respiration of the patient.

36. A cartridge configured to be connected to a delivery device for delivering an inhalation contrast agent to a patient by inhalation for pulmonary function and structural imaging, the cartridge comprising: a reservoir containing at least one dose of the inhalation contrast agent for delivery to the patient; and a closure for sealing the at least one dose of the inhalation contrast agent in the reservoir, wherein the closure is configured to open based on a signal received by the delivery device from a controller.

37. The cartridge according to claim 36, wherein, The controller is triggered to transmit the signal to the delivery device based on at least one of an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof.

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