NOBLE GAS DELIVERY DEVICE, CARTRIDGE, AND TRIGGERING SYSTEM FOR LUNG FUNCTIONAL AND STRUCTURAL IMAGING
CROSS REFERENCE TO RELATED APPLICATION
[0001] The present application is related to United States Patent Provisional Application Serial No. 63/518,344, filed August 9, 2023, the entire disclosure of which is hereby incorporated by reference in its entirety.
BACKGROUND OF THE DISCLOSURE
Field of the Disclosure
[0002] The present disclosure relates generally to delivery devices and systems for delivery of a diagnostic contrast composition ("‘contrast agent”) 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 lung imaging procedures.
Description of Related Art
[0003] There is often a medical need to assess one or more of ventilation, air trapping, physical structure, gas exchange, and perfusion status or capacity of the lungs or segments thereof in a patient, for example, in the case of pulmonary’ embolism, COPD (Chronic Obstructive Pulmonary Disease), or IPF (Idiopathic Pulmonary Fibrosis). The combination of these medical imaging needs above are hereafter summarized into the category of '‘functional and structural imaging”. In practice, this assessment may be done using nuclear medicine imaging technology, X-ray-based imaging technology, or magnetic resonance (MR) imaging technology. Lung assessment using nuclear medicine imaging technology may include Single Photon Emission Computed Tomography (SPECT) with an inhaled SPECT agent and/or with a blood pool SPECT agent. Lung assessment using X-ray imaging technology’ may include Computed Tomography (CT) imaging of the patient’s lungs while the patient is breathing xenon gas. The inhaled xenon gas may be imaged using CT as it dissolves in the patient’s blood at the alveoli of the lung, for example, to perform a functional and structural study of an organ or region of the body. Lung ventilation may be also assessed with MR imaging by’ having the patient breathe F-19 containing gases or hyperpolarized xenon gas. Lung functional and structural information may also be assessed using, for example, a gadolinium based intravenously’ injectable contrast agent. [0004] While these existing imaging modalities have a number of advantages for assessment of various lung characteristics, including function, condition, and disease state, they are also associated with a number of disadvantages. A typical dose of a SPECT imaging agent, such as 50mCi of rubidium-82 (2E+11 atoms) or lOmCi of flourine-18 (3.5E+12 atoms), allows collecting dynamic information without additional radiation exposure to the patient. While techniques based on nuclear medicine, including PET and SPECT, have high sensitivity and a single-dose radiation exposure, a drawback of these techniques is limited spatial resolution and relatively high image noise. A typical CT contrast dose of 100 ml of 370 mg of iodine per milliliter contrast corresponds to a dose of 6E+22 molecules and has the benefit of spatial resolution that is much higher than PET, with the temporal resolution being fractions of seconds. However, a drawback of CT technology is that an additional radiation dose is required for each image taken. With MR imaging, MR gadolinium contrast dosage is typically 10ml of ImMol/ml (about 6E+21 atoms of gadolinium). MR has the ability to image hyperpolarized atoms, with a sensitivity several orders of magnitude greater. For example, volumes on the order of milliliters of gas are needed for an imaging procedure using hyperpolarized xenon. But, like cyclotron produced radioactivity, hyperpolarization decays spontaneously and requires special and expensive equipment for its creation. While MR generally has spatial and temporal resolution between that of CT and nuclear medicine with no radiation dose to the patient, the gadolinium contrast is not readily transferred to the air and the MR receives no signal from air in the lungs as there are almost no hydrogen atoms to image relative to the hydrogen atom content of the surrounding tissue.
[0005] These modalities can make use of inhaled contrast for lung studies. However, conventional inhalation studies are complicated and involve the use of complex, expensive, and/or seldom-used machines. Therefore, these modalities are not used in common clinical practice for assessing ventilation and lung function. Even for pulmonary embolism, where the mainstay7 was once ventilation/perfusion (VQ) SPECT, CT angiography with intravenous injections of iodinated contrast media is now becoming the preferred modality. For these reasons, there is a need for convenient and easy-to-use delivery devices, systems, and methods for lung functional and structural imaging using inhaled contrast agents so that use of inhaled contrast agents for medical imaging can be more widely adopted.
SUMMARY OF DISCLOSURE
[0006] According to non-limiting embodiments, a cartridge configured for connection to a delivery device for delivery of an inhalation contrast agent to a patient via inhalation for lung functional and structural imaging is provided, including: a reservoir containing at least one dose of the inhalation contrast agent for delivery to the patient; and a closure sealing the at least one dose of the inhalation contrast agent in the reservoir, wherein the closure is configured to open in response to an insertion of the cartridge into the delivery device.
[0007] In some non-limiting embodiments, the inhalation contrast agent includes a noble gas such as at least one of the following: a hyperpolarized gas, xenon gas, krypton gas, or any combination thereof. In some non-limiting embodiments, the noble gas includes a sufficient quantity of atoms with an atomic number higher than 8 to provide an increased absorption sufficient to increase a Hounsfield Unit measurement in an image in a CT imaging system.
[0008] According to non-limiting embodiments, a delivery device for delivery of a gaseous contrast agent contained in a cartridge is provided including a reservoir containing at least one dose of an inhalation contrast agent for deliver}' to a patient via inhalation for lung functional and structural imaging, the deliver}7 device including: a housing defining an interior; a receptacle disposed in the interior of the housing, wherein the receptacle is configured to be connected to the cartridge to retain 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 an airway of the patient; 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 transition between a first position in which an interior of the reservoir of the cartridge is not in fluid communication with the outflow port and a second position in which 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 inhalation contrast agent to pass through the valve and the outflow' port to the airway of the patient.
[0009] According to non-limiting embodiments, a lung functional and structural imaging system is provided, including: an imaging device configured to obtain lung functional 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 a delivery device to deliver a dose of an inhalation contrast agent to the patient by inhalation; and control the imaging device to obtain at least one lung functional and structural image of the patient with the inhalation contrast agent in the lungs of the patient.
[0010] According to non-limiting embodiments, a method for imaging a lung of a patient is provided, including: delivering, with a delivery device containing a cartridge including a reservoir containing at least one dose of an inhalation contrast agent, a dose of the inhalation contrast agent to a patient; and following inhalation of the dose of the inhalation contrast agent and with the patient holding his or her breath, obtaining, with an imaging device, at least one lung functional and structural image of the patient.
[0011] According to non-limiting embodiments, a cartridge configured for connection to a deliver}' device for delivery' of an inhalation contrast agent to a patient via inhalation for lung functional and structural imaging is provided, including: a reservoir containing at least one dose of the inhalation contrast agent for delivery to the patient; and a closure sealing the at least one dose of the inhalation contrast agent in the reservoir, wherein the closure is configured to open based on the delivery' device receiving a signal from a controller.
[0012] In some non-limiting embodiments, the controller is triggered to transmit the signal to the delivery device based on at least one of the following: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof.
[0013] Various aspects of the present disclosure may be further characterized by one or more of the following clauses:
[0014] Clause 1 : A cartridge configured for connection to a delivery device for delivery’ of an inhalation contrast agent to a patient via inhalation for lung functional and structural imaging, comprising: a reservoir containing at least one dose of the inhalation contrast agent for delivery' to the patient; and a closure sealing the at least one dose of the inhalation contrast agent in the reservoir, wherein the closure is configured to open in response to an insertion of the cartridge into the delivery device.
[0015] Clause 2: The cartridge of clause 1 , wherein the inhalation contrast agent comprises a noble gas.
[0016] Clause 3: The cartridge of clause 1 or 2, wherein the noble gas comprises at least one of the following: a hyperpolarized gas, xenon gas. krypton gas, or any combination thereof.
[0017] Clause 4: The cartridge of clause 2 or 3, wherein the noble gas comprises a sufficient quantity of atoms with an atomic number higher than 8 to provide an increased absorption sufficient to increase a Hounsfield Unit measurement in an image in a CT imaging system.
[0018] Clause 5: The cartridge of any of clauses 1 to 4, wherein the reservoir defines a pressurized interior space containing the at least one dose of the inhalation contrast agent pressurized to a pressure above atmospheric pressure.
[0019] Clause 6: The cartridge of any of clauses 1 to 5, wherein the reservoir contains a single dose of the inhalation contrast agent effective for a single lung functional and structural imaging procedure. [0020] Clause 7. The cartridge of any of clauses 1 to 5, wherein the reservoir contains multiple doses of the inhalation contrast agent such that the cartridge can be used for multiple lung functional and structural imaging procedures.
[0021] Clause 8: The cartridge of any of clauses 1 to 7, wherein the cartridge is a disposable single-use cartridge.
[0022] Clause 9: The cartridge of any of clauses 1 to 7, wherein the cartridge is multi-use and recyclable.
[0023] Clause 10: The cartridge of any of clauses 1 to 9, wherein the closure comprises a pressure valve that maintains a pressure within a pressurized interior space of the reservoir at a pressure greater than 1.0 atm.
[0024] Clause 11 : A delivery device for delivery of a contrast agent contained in a cartridge including a reservoir containing at least one dose of an inhalation contrast agent for delivery to a patient via inhalation for lung functional and structural imaging, the delivery device comprising: a housing defining an interior; a receptacle disposed in the interior of the housing, wherein the receptacle is configured to be connected to the cartridge to retain 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 an airway of the patient; 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 transition between a first position in which an interior of the reservoir of the cartridge is not in fluid communication with the outflow port and a second position in which 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 inhalation contrast agent to pass through the valve and the outflow port to the airway of the patient.
[0025] Clause 12: The delivery device of clause 11, further comprising: a mechanical respirator configured to mechanically deliver the inhalation contrast agent from the interior of the reservoir of the cartridge to the airway of the patient.
[0026] Clause 13: The delivery device of clause 11 or 12, wherein a closure of the cartridge is configured to transition from a closed position, in which the at least one dose of the inhalation contrast agent is sealed within the interior of the reservoir of the cartridge, to an open position, in which the at least one dose of the inhalation contrast agent is enabled to flow from the interior of the reservoir of the cartridge, in response to a connection of the cartridge to the receptacle. [0027] Clause 14: The delivery device of any 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 passes through the valve and the outflow port to the airway of the patient, and when in the second position, the 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.
[0028] Clause 15: The deli ven' device of clause 14, wherein the valve is configured to remain in the second position for a predetermined period of time sufficient to deliver a dose of the at least one dose of the inhalation contrast agent to the patient and, following the predetermined period of time, automatically return to the first position.
[0029] Clause 16: A lung functional and structural imaging system, comprising: an imaging device configured to obtain lung functional 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 a delivery' device to deliver a dose of an inhalation contrast agent to the patient by inhalation; and control the imaging device to obtain at least one lung functional and structural image of the patient with the inhalation contrast agent in the lungs of the patient.
[0030] Clause 17: The lung functional and structural imaging system of clause 16, wherein the imaging device obtains the at least one lung functional and structural image during at least one of: an inhalation period, a breath-hold period, and an exhalation period.
[0031] Clause 18: The lung functional and structural imaging system of clause 16 or 17, further comprising the delivery' device for delivery' of the dose of the inhalation contrast agent to the patient, the delivery' device comprising: a housing defining an interior; a receptacle disposed in the interior of the housing, wherein the receptacle is configured to be connected to the cartridge to retain at least a portion of a cartridge within the housing; an outflow port extending through the housing, wherein the outflow port is configured to be positioned in fluid communication with an airway of the patient; and a 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 transition between a first position in which an interior of the reservoir of the cartridge is not in fluid communication with the outflow port and a second position in which 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 inhalation contrast agent to pass through the valve and the outflow port to the airway of the patient. [0032] Clause 19: The imaging system of clause 18, wherein the delivery device further comprises a mechanical respirator configured to mechanically deliver the inhalation contrast agent from the cartridge to the airway of the patient, and wherein the at least on controller is in electrical communication with the mechanical respirator and is configured to actuate the mechanical respirator to cause the dose of the inhalation contrast agent to be mechanically delivered from the cartridge to the patient at a predetermined time.
[0033] Clause 20: The imaging system of any 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 w ith the at least one controller, wherein the at least one controller is configured to control the at least one of the visual display, the audio output device, or any combination thereof to provide an instruction for the patient to hold his or her breath after inhalation of the inhalation contrast agent by the patient.
[0034] Clause 21: The imaging system of clause 20, wherein the at least one controller is further configured to control the at least one of the visual display, the audio output device, or any combination thereof to provide an instruction for the patient indicating that the patient should inhale the dose of the inhalation contrast agent with the delivery device at a predetermined time.
[0035] Clause 22: The lung functional and structural imaging system of any of clauses 18 to 21, wherein the delivery device comprises a hand-held manually operated inhaler.
[0036] Clause 23: The imaging system of any of clauses 16 to 22. further comprising: a fluid injector configured to deliver a dose of a vascular contrast agent to a vasculature of the patient. [0037] Clause 24: The imaging system of clause 23, wherein the at least one controller is configured to control the fluid injector to deliver the dose of the vascular contrast agent to the vasculature of the patient one of simultaneous with or in series with controlling the delivery device to deliver the dose of the inhalation contrast agent to the patient by inhalation.
[0038] Clause 25: The imaging system of any of clauses 16 to 24, wherein the mechanical respirator includes at least one sensor, and wherein the at least one sensor is configured to monitor breathing of the patient and provide feedback based on the monitored breathing of the patient to the at least one controller in electronic communication with the imaging device.
[0039] Clause 26: A method for imaging a lung of a patient, comprising: delivering, with a delivery device containing a cartridge comprising a reservoir containing at least one dose of an inhalation contrast agent, a dose of the inhalation contrast agent to a patient; and following inhalation of the dose of the inhalation contrast agent and with the patient holding his or her breath, obtaining, with an imaging device, at least one lung functional and structural image of the patient.
[0040] Clause 27: The method of clause 26, wherein delivering the dose of the inhalation contrast agent to the patient comprises expelling, with the delivery device, all or substantially all of the inhalation contrast agent from the reservoir for a single-use cartridge containing a single dose of the inhalation contrast agent.
[0041] Clause 28: The method of clause 26, wherein delivering the dose of the inhalation contrast agent to the patient comprises expelling, with the delivery device, a single dose of the inhalation contrast agent from the reservoir, wherein the reservoir contains multiple doses of the inhalation contrast agent.
[0042] Clause 29: The method of any of clauses 26 to 28. further comprising: controlling, with at least one processor, an output device to provide a breath-hold command to the patient after the patient inhales the inhalation contrast agent.
[0043] Clause 30: The method of any of clauses 26 to 29, further comprising: injecting, with a fluid injector, a vascular contrast agent to the patient simultaneous with or in series with causing the patient to inhale the dose of the inhalation contrast agent.
[0044] Clause 31 : The method of any of clauses 26 to 30, wherein delivering the dose of the inhalation contrast agent to the patient comprises controlling, with at least one processor, at least one of a visual display, an audio output device, or any combination thereof to provide an instruction to the patient to inhale the dose of the inhalation contrast agent from the delivery device, wherein the delivery device is a hand-held manually operated inhaler.
[0045] Clause 32: The method of any of clauses 26 to 31, wherein delivering the dose of the inhalation contrast agent to the patient comprises mechanically delivering, with a mechanical respirator, the dose of the inhalation contrast agent to the patient.
[0046] Clause 33: The method of clause 32, delivering the dose of the inhalation contrast agent to the patient comprises 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 the 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 disable the flow of the inhalation contrast agent from the delivery device to the patient.
[0047] Clause 34: The method of clause 33, wherein, w hen the valve is in the first position, at least one of ambient air, oxygen, or any combination thereof passes through the delivery device to the patient. [0048] Clause 35: The method of any of clauses 26 to 34, further comprising: monitoring, with at least one sensor, breathing of the patient; and controlling, with at least one processor, an output device to provide feedback based on the monitored breathing of the patient.
[0049] Clause 36: A cartridge configured for connection to a delivery device for delivery of an inhalation contrast agent to a patient via inhalation for lung functional and structural imaging, comprising: a reservoir containing at least one dose of the inhalation contrast agent for delivery to the patient; and a closure sealing the at least one dose of the inhalation contrast agent in the reservoir, wherein the closure is configured to open based on the delivery device receiving a signal from a controller.
[0050] Clause 37: The cartridge of clause 36, wherein the controller is triggered to transmit the signal to the delivery device based on at least one of the following: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof.
[0051] These and other features and characteristics of the contrast imaging agent, as well as the methods of operation and functions of the related elements of structures and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of w hich form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0052] FIG. l is a schematic drawing of a cartridge containing an inhalation contrast agent according to non-limiting embodiments of the present disclosure;
[0053] FIG. 2 is a schematic drawing of a delivery device for delivery of the contrast agent to a patient by inhalation, according to non-limiting embodiments of the present disclosure;
[0054] FIG. 3 is a schematic drawing of a system for lung functional and structural imaging using inhalation of a noble gas contrast imaging agent, according to non-limiting embodiments of the present disclosure; and
[0055] FIG. 4 is a flow chart showing a method for imaging a lung of a patient, according to non-limiting embodiments of the present disclosure.
[0056] It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only. DETAILED DESCRIPTION
[0057] For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the components as they are oriented in the drawing figures. When used in relation to a syringe, the term “proximal” refers to a portion of a syringe nearest a fluid injector when a syringe is oriented for connecting to a fluid injector. The term “distal” refers to a portion of a syringe farthest away from a fluid injector when a syringe and/or a plunger is oriented for connecting to a fluid injector. As used in the specification and the claims, the singular form of “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. The term “CT-active amount” refers to an amount of an X-ray contrast agent sufficient to get visualization of an X-ray contrast on a CT medical imager. The term “MR- active amount” refers to an amount of an MR contrast agent sufficient to get visualization on an MR medical imager. The term “airspace” refers to passages and gaseous space of the alveoli, the bronchiole, bronchi, trachea, and all other air containing structures of the lung. It is to be understood, however, that the disclosure may assume alternative variations and step sequences, except where expressly specified to the contrary. It is also to be understood that the specific devices and processes illustrated in the attached drawings, and described in the following specification, are simply exemplary aspects of the disclosure. Hence, specific dimensions and other physical characteristics related to the aspects disclosed herein are not to be considered as limiting.
[0058] As used herein, the term “computing device” may refer to one or more electronic devices configured to process data. A computing device may, in some examples, include the necessary components to receive, process, and output data, such as a processor, a controller, one or more displays, a memory, an input device, a network interface, and/or the like. A computing device may be a mobile device. As an example, a mobile device may include a cellular phone (e.g., a smartphone or standard cellular phone), a portable computer (laptop or pad), a wearable device (e.g., watches, glasses, lenses, clothing, and/or the like), a personal digital assistant (PDA), and/or other like devices. A computing device may also be a desktop computer or other form of non-mobile computer.
[0059] With reference to FIGS. 1-4, non-limiting embodiments of the present disclosure are directed to cartridges 10, devices 110, systems 210, and methods 400 for obtaining images of a lung of a patient using a noble gas, such as xenon gas (Xe) and/or krypton gas (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 “inhalation contrast agent”), for lung functional and structural imaging. For example, images of the lung with a dose of the inhalation contrast agent (e.g., a noble gas, etc.) within airspace of the lung can be obtained using a CT medical imager (e.g., a dual-energy CT imager, etc.), an MR medical imager, and/or the like.
[0060] The noble gas, xenon (Xe) is an inert gas and has an atomic number (54) that is close to that of iodine (53), such that its X-ray absorbance characteristics are very similar to that of iodine. In a similar manner, the noble gas krypton (Kr) also displays X- ray absorbance characteristics. In order to visualize the inhalation contrast agent, such as xenon gas or krypton gas, on a CT medical imager, the contrast agent should have sufficient contrast against the surrounding tissue in order to attenuate the X-ray beam from the CT medical imager. For CT imaging, attenuation is measured in Hounsfield Units (HU) which define radiodensity of a material at standard temperature and pressure. The image contrast that results depends upon the voltage (in kVp) of the X-ray tube. For example, the attenuation per mg I/mL of ULTRAVIST® 370 dissolved in blood is about 19 HU/mgL/ml at 140 kVp and 32 HU/mg I/mL at 90 kVp. The noble gases xenon and krypton will have sufficient X-ray attenuations to provide sufficient image contrast in CT imaging applications. Alternatively, hyperpolarization of the gas may allow the inhalation contrast agent to be MRI active and the procedures devices methods and embodiments described herein may be utilized in an MR imaging procedure of the air spaces of the lungs.
[0061] Non-limiting embodiments of the present disclosure are directed to containers or cartridges 10 that contain the dose(s) of the inhalation contrast agent to be provided to the patient, as well as to delivery devices 110, systems 210, and methods 300 for providing or delivering one or more of the dose(s) from the container or cartridge 10 to the patient via inhalation. For example, the delivery device 1 10 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 the inhalation contrast agent, such as a noble gas, to the patient's airway. In some examples, the cartridge 10 is a disposable, single use cartridge that is pre-filled with a single dose of the inhalation contrast agent. Alternatively, the cartridge 10 can contain multiple doses of the inhalation contrast agent, and the delivery device 110 can be configured to expel or release a desired amount for one dose of the inhalation contrast agent at an appropriate time, for example for multiple image procedures for a single patient or for providing a dose of the inhalation contrast agent to multiple patients during the course of the day.
[0062] Non-limiting embodiments of the present disclosure are directed to a system for lung functional and structural imaging using inhalation of a noble gas contrast imaging agent system 210, referred to herein as a “triggering system”, configured to control the delivery device 110 and one or more imaging devices to obtain the images of the patient's lung following inhalation of the inhalation contrast agent. The triggering system 210 may provide instructions or guidance for the patient during an imaging procedure, such as by providing a breath-hold and/or release instruction or command at an appropriate time during the procedure. The triggering system 210 may be configured to coordinate operation of other contrast injector devices and/or other imaging systems to obtain, for example, dual-energy CT imaging of different body regions or to control injection of a vascular imaging contrast agent, such as before, after or concurrent with the administration of the inhalation contrast agent.
[0063] FIG. l is a schematic drawing of a cartridge 10 containing one or multiple doses of an inhalation contrast agent comprising a noble gas inhalation contrast agent for delivery to a patient for lung functional and structural imaging, according to non-limiting embodiments of the present disclosure. As used herein, a cartridge 10 can refer to a sealed container configured to be inserted into and/or connected to a delivery device 110, for example by connection to a receptacle 116 of the delivery device 112, comprising a mechanism for opening or otherwise accessing the contents of the cartridge 10 and/or for expelling or releasing the noble gas from the cartridge 10 for delivery to the patient.
[0064] As shown in FIG. 1, the cartridge 10 comprises a container, barrel, or reservoir 12 configured to contain at least one dose of the inhalation contrast agent (e.g., a noble gas, etc.) for delivery to the patient. For example, the reservoir 12 can comprise a canister defining a pressurized interior sized to contain the single dose or multiple doses of the inhalation contrast agent. The cartridge 10 may include a closure 14 positioned over an opening 16 of the reservoir 12 that seals the reservoir 12 when the cartridge 10 is not in use (e.g., during transport, storage, or between uses of the cartridge 10). The closure 14 may be configured to open automatically when the cartridge 10 is inserted into the receptacle 116 of the delivery device 110. As an example, the closure 14 may be configured to transition from a closed position, in which the at least one dose of the inhalation contrast agent is sealed within the interior of the reservoir 12 of the cartridge 10, to an open position, in which the at least one dose of the inhalation contrast agent is enabled to flow from the interior of the reservoir 12 of the cartridge 10, in response to a connection of the cartridge to a receptacle 116 of the delivery7 device 110. As another example, the closure 14 may be configured to be opened based on receiving a control signal from system controller 218. For example, delivery device 1 10 may be configured to actuate a mechanism for piercing the closure 14 (e.g., a cannula, aneedle, a complementary' mating, etc.) or releasing the closure 14 from the cartridge 10 in response to receipt of a control signal from system controller 218. In such an example, system controller 218 may be triggered to transmit the control signal to the delivery device 110 based on at least one of the following: an input signal from an imaging device, a user selection, a fixed time delay, a patient signal, or any combination thereof. Alternatively, a user may manually open or remove the closure 14 immediately prior to inserting the cartridge 10 into the delivery device 110. In some examples, the closure 14 can be a septum 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 a system controller 218. Alternatively, or in addition, the closure 14 can comprise a valve, such as a pressure or crack valve, and/or the like, which maintains a pressure w ithin a pressurized interior space of the reservoir 12 at a minimum pressure above atmospheric pressure. For example, the minimum pressure can be 1.5 atm. 5.0 atm, 10.0 atm. or greater depending upon a structure of the cartridge 10, delivery device 110, and/or therapeutic requirements for 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 contain the single dose or multiple doses of the inhalation contrast agent. For example, the bag may be configured to be compressed or squeezed to deliver the noble gas contained in the reservoir 12 or the bag may' be configured to deliver the noble gas contained in the reservoir 12 in response to a negative pressure being applied thereto, such as in response to a negative pressure generated by a patient breathing in through the delivery device 110 when the cartridge 10 is connected to the delivery device 110. [0065] The cartridge 10 may be configured to contain any gas suitable for use as an inhalation contrast agent in lung functional and structural imaging. For example, as previously described, the gas can be a noble gas, such as a xenon gas, a krypton gas, or combinations thereof. For example, krypton gas may be used at higher concentrations compared to a concentration of xenon due to krypton gas having a lower opacity to x-rays than xenon gas. In some examples, the gas can be a hyperpolarized gas. In some examples, the noble gas comprises a sufficient quantity' of atoms with an atomic number higher than 8 to provide an increased absorption sufficient to increase a Hounsfield Unit measurement in an image in a CT imaging system. In some examples, the gas may include a mixture of oxygen and a noble gas, such as a xenon gas, a krypton gas, or combinations thereof. In other examples, the gas may include a mixture of air and a noble gas, such as a xenon gas, a krypton gas. or combinations thereof. Examples of injectable gaseous contrast agents comprising noble gases or other gases having X-ray opacity that could potentially be used with the cartridges, deliver}' devices, and systems disclosed herein are described in detail in U.S. Patent No. 11,576,985 which is incorporated herein by reference in its entirety.
[0066] According to certain embodiments, the cartridge 10 may be a disposable, single use cartridge 10 containing a single dose of the inhalation contrast agent to be delivered to the patient. In other examples, the cartridge 10 can be a reusable, refillable, and/or recyclable cartridge containing multiple doses of the inhalation contrast agent for use during multiple lung functional and structural imaging procedures. As used herein, a single dose of a noble gas refers to an effective amount of the noble gas for obtaining lung functional and structural images of suitable quality in accordance with the imaging technique being performed. For example, for X-ray imaging, the dose of noble gas in the reservoir 12 can be a CT-active amount, meaning an amount of the inhalation contrast agent sufficient to provide suitable visualization of an X- ray contrast on a CT medical imager. In a similar manner, for MR imaging, the dose of inhalation contrast agent in the reservoir 12 can be an MR-active amount of gas, meaning an amount of an MR contrast agent sufficient to provide visualization on an MR medical imager. [0067] FIG. 2 is a schematic drawing showing an embodiment of a delivery device 110 that receives cartridge 10 and controls release of the inhalation contrast agent, such as the noble gas, contained in the cartridge 10 for delivery of one or more doses of the contrast agent to a patient 124. For example, the cartridge 10 can be a removable and/or replaceable cartridge 10 that is inserted into the delivery device 110 prior to the imaging procedure and, in the case of a single dose cartridge 10. removed following completion of a lung functional and structural imaging procedure for the patient 124 or, in the case of a multi-dose cartridge, removed when the reservoir 12 of the cartridge 10 is empty. In some examples, inserting the cartridge 10 into the delivery' device 110 can cause the closure 14 of the cartridge 10 to automatically open or rupture, i.e., move to the second position. For example, the delivery device 110 can include a mechanism for piercing the closure 14 (e.g., a cannula, aneedle. a complementary mating, etc.) or releasing the closure 14 from the cartridge 10 to access the noble gas contained in the reservoir 12.
[0068] As illustrated in FIG. 2, the drug delivery' device 110 comprises a housing 112 defining an interior sized to receive at least a portion of the cartridge 10. For example, the housing 112 may be a cylindrical-, box-, or other shaped enclosure including a port or opening 114 configured for insertion of the cartridge 10 into the housing 112. The delivery device 110 may include a receptacle 1 16 disposed in the interior of the housing 112, such as at a distal end of the opening 114, that retains at least a portion of the cartridge 10 and closure 14 within the housing 112. For example, the receptacle 116 may be configured to be connected to the cartridge to retain at least a portion of the cartridge within housing 112. For example, the receptacle 116 and/or the cartridge 10 can include locking features (e.g., a Luer lock mechanism, bayonet lock mechanism, screw-lock mechanism, etc.) for connecting the cartridge 10 to receptacle 116 of the delivery device 110, as well as mechanisms (e.g., a cannula, a needle, a complementary mating, etc.) for opening the closure 14 or accessing the gaseous contents of the cartridge 10 and for expelling the noble gas contained therein from the reservoir 12 and to the patient 124.
[0069] The delivery device 110 may further comprise an outflow port 118 connecting to a delivery feature (patient accessory 126), such as a mouthpiece, respiratory mask, nozzle, and/or the like, extending through the housing 112 configured to be positioned in fluid communication with an airway of the patient 124. In some examples, the patient 124 may position the mouthpiece, respiratory mask, or nozzle in their mouth for delivery of the dose of the inhalation contrast agent directly to the patient’s airway. In other examples, the dose of the inhalation contrast agent can be delivered to the patient’s airway through a patient accessory 126, such as a mask, nasal cannula, breathing tube, or similar device, connected to the outflow port 118 of the delivery device 1 10 by, for example, flexible tubing 128.
[0070] The delivery device 110 may further comprise a valve 120 between the receptacle 116 (and the cartridge 10) and the outflow' port 118. For example, the receptacle 116 may be configured to place the cartridge 10 (e.g.. the interior of reservoir 12 of cartridge 10, etc.) in fluid communication with the valve 120 when the cartridge 10 is connected to or engaged with the receptacle 116. As an example, the valve 120 may be configured to transition between a first position in which the interior of the reservoir 12 of the cartridge 10 is not in fluid communication with the outflow port 118 and a second position in which the interior of the reservoir 12 of the cartridge 10 is in fluid communication with the outflow port 118 to enable the at least one dose of the inhalation contrast agent to pass through the valve 120 and the outflow' port 118 to the airway of the patient. For example, the valve 120 may be configured to transition between a first or closed position sealing the dose(s) of the inhalation contrast agent in the reservoir 12 of the cartridge 10 and a second or open position in which the dose(s) of the inhalation contrast agent pass through the valve 120 and outflow port 118 to the airway of the patient 124. In some examples, the valve 120 can be configured to transition between providing ambient air (e.g., room, atmospheric, etc.) or oxygen to the patient 124 and providing the inhalation contrast agent from the cartridge 10 to the patient 124. For example, as shown in FIG. 2, the valve 120 can be configured such that, when in the closed position, the ambient air or oxygen passes through the valve 120 and outflow port 118 to the airway of the patient 124, as shown by arrows Al in FIG. 2. When the valve 120 is in the open position, the ambient air or oxygen may be prevented from passing through the valve 120 and outflow port 118. Instead, when the valve 120 is in the open position, the inhalation contrast agent passes from the cartridge 10 to the patient's airway through the valve 120 and outflow port 118 as shown by arrows A2 in FIG. 2. In some examples, the valve 120 can be configured to remain in the open position for only a predetermined period of time after which the valve 120 is automatically closed. For example, the valve 120 can be configured to open for a predetermined period of time sufficient to deliver a single dose of contrast agent to the patient 124 and, following the predetermined period of time, can automatically return to the closed position. In certain embodiments, the valve 120 may provide a mixture of ambient air/oxygen and the inhalation contrast agent, for example to control the concentration of the dosage of inhalation contrast agent. As previously described, with the valve 120 in the closed position the ambient air or oxygen can be delivered to the patient 124 through the outflow port 118 or mouthpiece.
[0071] In some embodiments, the valve 120 may include a two-way valve. For example, a first input of the valve 120 may be connected to the receptacle 1 16 and a second input of the valve 120 may be connected to the ambient air or an oxygen source. In some implementations, the valve 120 may include a three-way valve. For example, a first input of the valve 120 may be connected to the receptacle 116, a second input of the valve 120 may be connected to the 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 the valve 120 to switch between connecting one or more of the inputs to the outflow port 218 according to user input and/or an inhalation contrast delivery protocol.
[0072] The delivery device 110 may be a manually activated device or an automated device. For example, the delivery device 110 can be a handheld or portable inhaler that can be activated when a user, such as the patient 124, presses a release button or similar mechanism for opening the valve 120. The release button may also activate, for example, a piston, a plunger, or similar compression mechanism for forcing the dose of the inhalation contrast agent from the reservoir 12 of the cartridge 10. Alternatively, the inhalation contrast agent may be pressurized within cartridge 10 at a pressure greater than atmospheric pressure such that upon activation, the inhalation contrast agent flows to the patient due to release of pressure.
[0073] With continued reference to FIG. 2, the 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 breaths with dose(s) of the inhalation contrast agent or utilizing pressure release of the pressurized inhalation contrast agent to the airway of the patient 124. Upon activation of the respirator 122 or similar device, the dose of the contrast agent can be drawn from the reservoir 12 of the cartridge 10 and delivered to the patient as one or more mechanical breaths.
[0074] FIG. 3 is a schematic drawing showing a lung functional and structural imaging system 210, according to non-limiting embodiments of the present disclosure, which can be used with the cartridges 10 and delivery devices 110 of the present disclosure. As previously described, the system 210 may be configured to coordinate release of the inhalation contrast agent from the delivery device 110 for inhalation by the patient 124, image scanning of the patient’s lung(s) with one or more imaging devices, and any other imaging techniques or processes that may be performed for the patient simultaneous or in sequence with the lung functional and structural imaging process. As previously described, images captured by the system 210 may be used to assess one or more of the ventilation, air trapping, physical structure, gas exchange, perfusion status, or capacity of the lungs or segments of the patient’s lungs.
[0075] As shown in FIG. 3, the system 210 may comprise an imaging device 212 configured to obtain lung functional and structural images of the patient 124. For example, the imaging device 212 can be a CT medical imager for use with X-ray contrast and/or an MR imager using, for example, a hyperpolarized noble gas. An exemplary imaging device 212, which can be used to obtain images of multiple contrast agents and/or different functional areas of a patient’s body and which can be used with the systems 210 and methods 300 disclosed herein, is described in U.S. Patent Appl. Pub. No. 2022/0401588 to Flohr et al., which incorporated by reference herein in its entirety. The system 210 can further comprise the delivery device 110 for delivering the contrast agent from a cartridge 10 containing the appropriate contrast agent to the patient 124 via inhalation. As previously described, the delivery device 110 can be a manual device, such as a hand-held inhaler, or an automated delivery device, such as a respirator 122 or ventilator. [0076] In some examples, the system 210 may further comprise 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 patient. For example, the system 210 can include an input device 214, such as a terminal, a user interface, a keyboard or touchscreen display, and/or the like that enables the user to enter information about the patient 124 and/or procedure being performed. The system 210 can include an output component, such as a visual display 216, an audio output component, and/or the like for providing information and instructions to the system user and/or patient 124.
[0077] With continued reference to FIG. 3, the system 210 further comprises a controller 218, such a computing device or computer processor, in electrical communication with one or more of imaging device 212, delivery device 110, and/or other system 210 components. The controller 218 may be configured to coordinate delivery of the inhalation contrast agent, vascular contrast agents, and/or image scanning to obtain lung functional and structural images. For example, the controller 218 can be configured to cause a dose of the inhalation contrast agent to be administered from the delivery device 110 to the patient 124. The controller 214 can be configured, following inhalation of the dose of the inhalation contrast agent by the patient 124, to cause the imaging device 212 to obtain a lung functional and structural image of the patient with the inhalation contrast agent in lungs of the patient 124. In certain procedures, the controller 214 may also be configured to control or manage injection of a vascular contrast agent from fluid injector 220, as described herein.
[0078] In some examples, imaging of the lung(s) of patient 124 can be performed during at least one of: an inhalation period (e.g., a period of time during which the patient 124 is inhaling the dose of the inhalation contrast agent into their lungs), a breath-hold period (e.g.. a period of time during which the patient 124 holds the dose of the inhalation contrast agent in their lungs without inhaling or exhaling), an exhalation period (e.g., a period of time during which the patient 124 is exhaling the dose of the inhalation contrast agent out of their lungs), a period before the inhalation period or after the exhalation period (e.g., when the patient 124 is in the imaging device 212 but without the inhalation contrast agent in the lungs), or any combination thereof. Further, in some examples, the controller 218 can be configured to cause the imaging device 212 to obtain or capture a sequence of lung images. For example, the controller 218 can be configured to cause the imaging device 212 to obtain multiple images at different times according, for example, to a lung functional and structural imaging protocol. For example, in an exemplary imaging protocol, the controller 218 may be configured to cause the imaging device 212 to obtain a first image of the lungs immediately or shortly after (e.g., within 1 second to 10 seconds) inhalation of the inhalation contrast agent by the patient 124 and, following a breath-hold period of other predetermined delay time (e.g., a delay of 30 seconds, 1 minute, 5 minutes, or longer), obtain second or delayed images of the lungs to show changes in contrast agent concentration within airspace of the lungs over time.
[0079] When the delivery device 110 is an automated or mechanical delivery device, such as a respirator 122 or ventilator, the controller 218 may be configured to control the delivery device 110 so that the dose of inhalation contrast agent is delivered at an appropriate time before the lung image is obtained. For example, the controller 218 can be configured to actuate the delivery device 110 and to cause the imaging device 212 to obtain the functional and structural images a predetermined period of time (e.g., 1 second. 2 seconds. 5 seconds. 10 seconds, or longer) after the contrast agent is inhaled by the patient, for example during a breath-hold period. The controller 218 may be configured to provide an instruction to the patient on the visual display 216 or auditory output instructing the patient when to breathe and/or hold his or her breath as the inhalation contrast agent is being provided. For example, an instruction for the patient 124 to hold their breath after inhaling the contrast agent can be displayed on the visual display 216, so that the contrast agent remains in the patient’s lungs for at least the predetermined period of time.
[0080] When the delivery device 110 is a manually activated or controlled device (e.g., a handheld or portable inhaler, etc.), instructions for when to use the inhaler can be displayed or announced, for example, on the visual display 216 or auditory output device of the system 210. For example, the controller 218 can be configured to cause an instruction to “Inhale Now” or “Take Deep Breath” to be displayed on the visual display 216 informing the patient 124 when to use the inhaler device 110. An instruction for the patient to hold his or her breath after inhaling the inhalation contrast agent may also be displayed on the visual display 216. As in previous examples, the controller 214 can be configured to cause the imaging device 212 to obtain the functional and structural images of the patient’s lungs a predetermined period of time (e g., 1 second, 2 seconds, 5 seconds, 10 seconds, or longer) after the instruction to inhale the contrast agent is displayed.
[0081] With continued reference to FIG. 3, the system 210 can further comprise another delivery device, such as a manually operated or powered fluid injector 220, for delivering another diagnostic vascular contrast agent to, for example, the patient’s bloodstream (referred to herein as a “vascular contrast agent”). For example, the fluid injector 220 can be configured to deliver an effective amount of the vascular contrast agent (e.g., CT imaging contrast, MR imaging contrast, tungsten, etc.) from a container or syringe mounted to the fluid injector 220 to the vasculature of the patient 124 through a disposable set or catheter assembly. Exemplary syringes and powered fluid injectors suitable for use as 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 by reference in its entirety.
[0082] In some examples, the fluid injector 220 for the vascular contrast agent can be a multi-syringe injector, wherein two or more syringes may be oriented in a side-by-side or other arrangement and include plungers separately actuated by respective pistons associated with the injection. The fluid injector 220 can be configured to receive a syringe filled with the vascular contrast agent and one or more additional syringes filled with different fluids, such as saline or another vascular contrast agent, and the fluid injector 220 may be used to deliver the saline and/or vascular contrast composition(s) into the patient 124. The delivery of fluid from the multiple syringes can be controlled by the fluid injector 220 and/or controller 218. Fluid flow from the syringes may be regulated by a fluid control module (not shown) of the fluid injector 220. The fluid control module may operate various pistons, valves, and/or flow regulating structures of the fluid injector 220 to regulate the delivery of the medical fluid, such as saline solution and the vascular contrast agent, to the patient 124 based on user selected injection parameters, such as injection flow rate, duration, total injection volume, and/or ratio of contrast media and saline. Other examples of relevant multi-fluid delivery' systems that may be modified for use with the present systems 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 Appl. Pub. No. WO 2012/155035, the disclosures of w hich are incorporated herein by reference.
[0083] The controller 218 can also be in electrical communication with the fluid injector 220, in addition to other components of lung functional and structural imaging system 210, and can be configured to coordinate fluid delivery by the fluid injector 220 with delivery' of the inhalation contrast agent by 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 vascular contrast agent to the vasculature of the patient 124 before, simultaneous with or substantially simultaneous with (e.g., within 1 second to 5 seconds of, etc.), or after, causing an effective dose of the inhalation contrast agent to be administered from the delivery device 110 to lungs of the patient 124 by inhalation. As an example, controller 218 may control fluid delivery by the fluid injector 220 to occur earlier than the delivery of the inhalation contrast agent (e.g., 15 minutes before, 30 minutes before) so that the imaging device 212 can obtain functional and structural images showing each of the contrast agent inhaled in the lungs and the vascular contrast agent in vasculature of the patient 124 in one scan with both the lungs full of inhalation contrast agent and the vascular contrast agent fully in the blood of the patient. In another example, simultaneous administration of the vascular contrast agent from the fluid injector 220 and the inhalation contrast agent from the delivery device 110, the controller 218 can be configured to cause the imaging device 212 to obtain functional and structural images showing each of the contrast agent inhaled in the lungs and the vascular contrast agent in vasculature of the patient 124, for example as the vascular contrast agent spreads throughout the vasculature of the patient 124.
[0084] The cartridge 10, delivery devices 110, and triggering system 210 disclosed herein may be used in methods for imaging a lung of a patient 124. Generally, for diagnostic imaging procedures, the patient 124 is placed on an imaging platform, usually lying flat on the back, side, or stomach for a duration of the imaging procedure. For some lung imaging, however, it may be desirable for the patient to be in the upright position.
[0085] Referring now to FIG. 4, shown is a flow diagram for a method 400 for imaging a lung of a patient, according to non-limiting embodiments of the present disclosure. The steps shown in FIG. 4 are for example purposes only. It will be appreciated that additional, fewer, different, and/or a different order of steps may be used in some non-limiting embodiments or aspects. In some non-limiting embodiments, a step may be automatically performed in response to performance and/or completion of a prior step.
[0086] As illustrated in FIG. 4, at step 402, method 400 includes delivering, with a delivery device 110, a dose of an inhalation contrast agent to a patient 124. For example, delivery device 110 containing cartridge 10 comprising reservoir 12 containing at least one dose of an inhalation contrast agent may deliver a dose of the inhalation contrast agent to patient 124. For example, the patient 124 may be instructed to inhale a dose of the inhalation contrast agent, as described herein, with the delivery device 110. As previously described, the inhalation contrast agent can be contained in a removable and/or replaceable cartridge 10 (e.g., a single, use prefilled cartridge containing a single dose of the inhalation contrast agent, a multi-use cartridge containing multiple doses of the contrast agent, etc.) inserted into the delivery device 110. For a single use cartridge, the method 400 can include expelling all or substantially all (e.g., a predetermined percentage, etc.) of the noble gas from the reservoir 12 of the cartridge 10 to the patient 124. For a cartridge 10 containing multiple doses of the inhalation contrast agent, the method 400 can include controlling a valve 120, respirator 122, closure 14, and/or similar component of the delivery device 110 or cartridge 10 so that a desired amount (e.g., a single dose or each dose of the multiple doses) of the inhalation contrast agent is expelled from the reservoir 12 of the cartridge 10 at an appropriate time.
[0087] The delivery device 110 can be either an automated delivery device (e.g., 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 the dose of the inhalation contrast agent can include actuating the respirator 122 and moving valve 120 to the open position so that the inhalation 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 ensuring that a correct amount of the inhalation contrast agent is delivered to the patient 124. For a manual delivery device, delivering the dose of the inhalation contrast agent can include instructing the patient to use the inhaler and/or assisting the patient in use of the inhaler at an appropriate time.
[0088] As shown in FIG. 4, at step 404, method 400 includes providing an instruction to the patient to hold his or her breath. F or example, system controller 218 may control visual display 216 and/or an 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 inhalation contrast agent, system controller 218 may receive, from delivery’ device 110 an indication that the dose of the inhalation contrast agent has been delivered and, in response to receiving the indication that the inhalation contrast agent has been delivered, provide an instruction to the patient to hold his or her breath so that the inhalation contrast agent remains in the airspace of the patient’s lungs. For example, as previously described, a breath-hold instruction or command can be displayed on the visual display 216 or emitted from an auditory output device of the system 210.
[0089] As shown in FIG. 4. at step 406. method 400 includes optionally injecting a vascular contrast agent to vasculature of the patient, for example in an imaging procedure that incorporates both the administration of the inhalation contrast agent and injection of a vascular contrast agent. For example, fluid injector 220 (e.g., in response to a command from system controller 218. in response to a user input, etc.) may inject a vascular contrast agent into vasculature of the patient 124 prior to, simultaneous or substantially simultaneous with, and/or after delivering the dose of the inhalation contrast agent to the patient 124. For example, the vascular contrast agent can be injected by actuating the fluid injector 220, causing the vascular contrast agent to pass from the fluid injector 220 through a catheter set or assembly into the patient's bloodstream.
[0090] As shown in FIG. 4, at step 408, method 400 includes obtaining a lung functional and structural image of the patient. For example, imaging device 212 may obtain a lung functional and structural image of the patient 124. As an example, following inhalation of the dose of the inhalation contrast agent, and optional injection of vascular contrast agent, and with the patient 124 holding his or her breath, a lung functional and structural image of the patient 124 may be obtained with imaging device 212. The images can be obtained prior to, simultaneous or substantially simultaneous with, and/or after delivering the dose of the inhalation contrast agent or following a predetermined delay (e.g., a delay for 5 seconds to 15 seconds, etc.). In some examples, the imaging device 212 can be used to collect one or more consecutive images while the 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-hold phrase, such as after 5 seconds to 15 seconds, the imaging device 212 can continue to collect images as the patient 124 takes one or more breaths showing how the inhalation contrast agent washes out from the lungs. In certain embodiments, the method can include obtaining a second series of lung functional and structural images a predetermined period of time (e.g., from 1 minute to 30 minutes) after an initial series of lung functional and structural images is obtained to visualize an amount of contrast agent in airspace of the lungs after the predetermined period of time.
[0091] In some examples, the method 400 comprises obtaining multiple images of the 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, the breath-hold phase (e.g., as the patient holds their breath with the contrast agent in their lungs), and an exhalation phase (e.g.. as the inhalation contrast agent washes out of the lungs). For example, the imaging protocol can include taking one or multiple images of the patient’s lungs during the inhalation phase. The imaging protocol can include taking one or multiple images during a breath-hold phase, such as a breath-hold phase lasting from about 5 seconds to about 30 seconds following inhalation of the contrast agent. The imaging protocol may include taking one or multiple images during the exhalation phase when the patient 124 breathes out. The images can be taken after a predetermined period and/or at a predetermined constant or variable spacing, such as 2 seconds, 5 seconds, 10 seconds, to about 30 seconds, to a total time of about 5 minutes after the breath-hold phrase to allow the gas to be washed substantially completely out from the patient’s lungs. In some examples, the method can also include taking one or more high-dose, high-resolution scans, and one or more low-dose, lower resolution scans for dynamic data. The image acquisition and analysis may be similar, for example, to those done in PET and SPECT. [0092] As previously described, the imaging device 212 may include a CT medical imager and/or an MR imager, depending upon the type of inhalation contrast agent being used. Further, when contrast agent is provided to each of the airspace of the lungs and to the patient vasculature, the imaging device 212 can be configured to detect or visualize each of the contrast agents. For example, the imaging device 212 can be a dual-energy CT imager configured to obtain images visualizing each of the noble gas in the lungs and the vascular contrast agent in the patient’s bloodstream.
[0093] Although the disclosure has been described in detail for the purpose of illustration based on what are currently 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 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.