Systems, methods, compositions and devices for in vivo magnetic resonance imaging of lungs using perfluorinated gas mixtures

• US 9,724,015 B2
• Filed: 01/04/2016
• Issued: 08/08/2017
• Est. Priority Date: 02/16/2010
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Charles, Hal Cecil, Soher, Brian J.
• Primary Examiner(s): Smith, Ruth S
• Application Number:
  US14/987,356
• Publication Number:
  US 20160113548A1
• Time in Patent Office: 582 Days
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2576/02 specially adapted for a particular organ or body part
• CPC Class Codes: A61B 5/0033 Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room image data processing or generation G06T
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/08 Detecting, measuring or recording devices for evaluating the respiratory organs A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/0813 Measurement of pulmonary parameters by tracers, e.g. radioactive tracers
• CPC Class Codes: A61B 5/082 Evaluation by breath analysis, e.g. determination of the chemical composition of exhaled breath A61B5/083, A61B5/091 take precedence
• CPC Class Codes: A61B 5/087 Measuring breath flow
• CPC Class Codes: A61B 5/7285 for synchronising or triggering a physiological measurement or image acquisition with a physiological event or waveform, e.g. an ECG signal A61B6/5205, A61B6/541, A61B8/5207, A61B8/543 take precedence
• CPC Class Codes: A61M 16/0054 Liquid ventilation
• CPC Class Codes: A61M 16/085 Gas sampling
• CPC Class Codes: A61M 16/1055 bacterial
• CPC Class Codes: A61M 16/107 in the inspiratory path
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 2016/1025 the O2 concentration
• CPC Class Codes: A61M 2202/0476 Oxygenated solutions
• CPC Class Codes: A61M 2230/432 partial CO2 pressure (P-CO2)
• CPC Class Codes: A61M 2230/435 partial O2 pressure (P-O2)
• CPC Class Codes: G01R 33/50 based on the determination of relaxation times , e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: G01R 33/56325 : Cine imaging
• CPC Class Codes: G01R 33/56366 : Perfusion imaging
• CPC Class Codes: G01R 33/5673 : Gating or triggering based on a physiological signal other than an MR signal, e.g. ECG gating or motion monitoring using optical systems for monitoring the motion of a fiducial marker

Abstract

Systems and methods for generating MRI images of the lungs and/or airways of a subject using a medical grade gas mixture comprises between about 20-79% inert perfluorinated gas and oxygen gas. The images are generated using acquired ¹⁹F magnetic resonance image (MRI) signal data associated with the perfluorinated gas and oxygen mixture.

Claims

1. A method of generating lung ventilation information of a subject, comprising:

providing a pressurized canister of a medical grade gas mixture of perfluorinated gas and oxygen holding the medical grade mixture in a gaseous phase;

electronically obtaining a series of ¹⁹F magnetic resonance imaging (MRI) images of lungs of a subject associated with an inhaled amount of the perfluorinated gas and oxygen mixture from the pressurized canister during wash in and wash out of the perfluorinated gas and oxygen mixture;

electronically obtaining ¹H MRI images of the lungs of the subject before or after or before and after obtaining the series of ¹⁹F MRI images while the subject breathes room air;

electronically registering the obtained ¹⁹F MRI lung images to the obtained ¹H MRI lung images of the subject;

electronically applying lung masks to the registered ¹⁹F images to define a perimeter of a lung cavity of a respective lung; and

then

electronically evaluating summary parameters of different volumes of the registered ¹⁹F lung images after applying the lung masks to generate lung ventilation information that identifies regional lung ventilation defects including gas trapping,

wherein the obtaining, registering, applying and evaluating steps are carried out using at least one processor.

2. The method of claim 1, wherein the electronically evaluating the summary parameters evaluates 2D shape factors of the different volumes.

3. The method of claim 1, further comprising displaying a series of color-coded static lung images showing regional ventilation information over at least a portion of at least one respiratory cycle based at least in part on the evaluated summary parameters.

4. The method of claim 1, further comprising displaying lung ventilation information on a color-coded lung map of ventilation and/or perfusion with at least one of abnormalities, defects and deficiencies shown with at least one of a defined color(s), intensity or opacity based on the summary parameters to thereby make the at least one of the abnormalities, defects and deficiencies visually dominant.

5. The method of claim 1, further comprising electronically displaying a graph of ¹⁹F pixel intensity versus pixel count for each lung based on the pixels in the different volumes and different slices.

6. The method of claim 1, further comprising generating histograms of mean intensity of voxels within regions of interest to identify clusters of voxels or those that have a statistically significant variance from normal intensity voxels.

7. The method of claim 1, wherein the electronically evaluating comprises electronically generating data tables of pixel parameters for the different volumes with the tables comprising pixel centroids for respective slices in the different volumes.

8. The method of claim 1, further comprising electronically providing a visual output of a graphic analysis fit to a lung model of ventilation wash-in and wash-out using the obtained ¹H and ¹⁹F MRI images and depicting functional information based on the summary parameters.

9. The method of claim 1, further comprising displaying a lung map as a rendered visualization of one or more selected summary parameters that shows at least one of ventilation and perfusion information in a manner that illustrates relative degrees or measures of function in at least one of different colors, opacities and intensities.

10. The method of claim 1, further comprising displaying three dimensional fusions of the obtained ¹H and ¹⁹F MRI images, color-coded to show ventilation defects based on the summary parameters.

11. The method of claim 1, wherein the medical grade gas mixture is supplied at a pressure in the pressurized canister that is sufficiently low so that a dense gas component remains in a gaseous state under normal operating conditions of at least one of about 21 degrees C. or room temperature.

12. The method of claim 1, wherein the electronically evaluating the summary parameters evaluates a plurality of the following:

pixel intensity, pixel count, histograms, summary statistics and 2-D shape factors.

13. The method of claim 1, wherein the electronically evaluating the summary parameters evaluates histograms of pixel intensity versus pixel count to identify ventilation defects.

14. The method of claim 1, further comprising quantitatively analyzing lung function and/or electronically assessing regional ventilation of the lungs and providing a visualization of a map of the lungs illustrating regional ventilation defects of the lungs.

15. The method of claim 1, further comprising quantitatively evaluating gas trapping by cycling between administration of the medical grade oxygen and gas mixture and administration of room air to the subject, wherein loss of ¹⁹F MRI signal over time associated with the different volumes and different slices during the cycling corresponds to a measure of gas trapping.

16. A method of obtaining lung information of a subject, comprising:

positioning a subject in a magnetic field associated with a high-field magnet of an MRI scanner;

cyclically delivering, in vivo, via inhalation, a medical grade gas mixture and room air to the subject while the subject is in the magnetic field of the MRI scanner, wherein the medical grade gas mixture comprises between 20-79% inert perfluorinated gas and at least 20.5% oxygen gas obtained from a pressurized canister of the medical grade gas mixture, wherein the medical grade gas mixture is supplied at low pressure in the pressurized canister so that a dense gas component remains in a gaseous state under normal operating conditions of about 21 degrees C. and/or room temperature;

electronically acquiring a series of ¹⁹F MRI lung space images associated with the inhalation of the cyclically delivered medical grade gas mixture and a series of ¹H MRI lung images, wherein the series of ¹⁹F MRI lung space images includes images acquired while the subject breathes room air to obtain wash-out and/or gas trapping data associated with a deplenishing amount of the ¹⁹F MRI signal as the subject breathes room air, and wherein the series of ¹H MRI lung images are acquired using the room air delivered to the subject before or after acquiring the series of ¹⁹F MRI lung space images or before and after acquiring the series of ¹⁹F MRI lung space images;

registering the acquired ¹⁹F MRI lung images to the acquired ¹H MRI lung images of the subject;

applying lung masks to the registered ¹⁹FMRI images to define a perimeter of a lung cavity of a respective lung; and

then

evaluating summary parameters by slice of a plurality of different volumes of the registered ¹⁹FMRI lung images after applying the lung masks to generate lung ventilation information that identifies regional lung ventilation defects including gas trapping,

wherein the acquiring, registering, applying and evaluating are carried out using at least one processor.

17. The method of claim 16, wherein the cyclical delivering is carried out so that a component ratio of the medical grade gas mixture that is drawn out of the pressurized canister remains constant, the method further comprising providing the pressurized canister with the medical grade gas mixture at the low pressure for the cyclical delivering with the medical grade gas mixture formulated to have a dew point of 0 degrees C. so that the medical grade gas mixture will not condense above this temperature.

18. The method of claim 16, wherein the evaluating the summary parameters evaluates a plurality of the following:

pixel intensity, pixel count, histograms, summary statistics and 2-D shape factors.

19. The method of claim 18, further comprising electronically generating and displaying a visual output of a graphic analysis using the acquired ¹⁹F MRI images fit to a lung model of ventilation wash-in and wash-out depicting functional information of one or both lungs of the subject.

20. The method of claim 18, further comprising generating histograms of mean intensity of voxels within regions of interest to identify clusters of voxels that have a statistically significant variance from normal intensity voxels.

21. The method of claim 20, further comprising electronically evaluating the histograms to identify whether the subject is likely to have a ventilation and/or lung defect.

22. An MRI system, comprising:

an MRI scanner comprising a magnet with a magnetic field and at least one RF coil, the at least one RF coil being sized and configured to reside about lungs of a human patient; and

a gas delivery system comprising;

a pressurized canister of a medical grade gas mixture comprising perfluorinated gas in a level that is between 20-79% and oxygen gas in a level that is at least 20.5%, wherein the pressurized canister is at a sufficiently low pressure to hold the gas mixture in a gaseous state at room temperature;

a gas flow path in communication with the pressurized canister of the medical grade gas mixture comprising at least one conduit extending from the canister to a free-breathing dispensing member adapted to reside over, on or in a respective patient while the patient resides inside the magnetic field to deliver the medical grade gas mixture;

at least one oxygen sensor in communication with the gas flow path of the medical grade gas mixture; and

at least one processor in communication with and/or onboard the MRI scanner, wherein the at least one processor;

(i) obtains a series of ¹⁹F magnetic resonance imaging (MRI) images of lungs of the patient associated with the medical grade gas mixture during wash in and wash out of the perfluorinated gas and oxygen mixture;

(ii) obtains ¹H MRI images of the lungs of the patient associated with room air inhaled by the patient before or after or before and after the series of ¹⁹F magnetic resonance imaging (MRI) images of lungs of the patient are obtained;

(iii) registers the obtained ¹⁹F MRI lung images to ¹H MRI lung images of the patient;

(iv) applies lung masks to the registered ¹⁹F images to define a perimeter of a lung cavity of a respective lung; and

then

(v) evaluates summary parameters from a plurality of slices of a plurality of different volumes of the registered ¹⁹F lung images after the lung masks are applied to generate lung ventilation information that identifies regional lung ventilation defects including gas trapping.

23. The system of claim 22, wherein the evaluated summary parameters comprise 2D shape factors of the slices of the different volumes.

24. The system of claim 22, wherein the at least one processor determines a time constant for the medical grade gas mixture to calibrate signal intensity based on a sample of an input of the delivered gas mixture and an exhaled sample of the delivered gas mixture to thereby define a global exchange of oxygen.