	US 11,944,424 B2
	Dynamic 129Xe gas exchange spectroscopy
Elianna Bier, Durham, NC (US); Bastiaan Driehuys, Chapel Hill, NC (US); Ziyi Wang, Durham, NC (US); and Sudarshan Rajagopal, Chapel Hill, NC (US)
Assigned to Duke University, Durham, NC (US)
Filed by Duke University, Durham, NC (US)
Filed on May 8, 2019, as Appl. No. 16/406,630.
Claims priority of provisional application 62/673,175, filed on May 18, 2018.
Prior Publication US 2020/0022616 A1, Jan. 23, 2020
Int. Cl. A61B 5/08 (2006.01); A61B 5/00 (2006.01); A61B 5/055 (2006.01); G01R 33/54 (2006.01); G16H 30/40 (2018.01)

CPC A61B 5/0813 (2013.01) [A61B 5/055 (2013.01); A61B 5/7282 (2013.01); G01R 33/543 (2013.01); G16H 30/40 (2018.01); A61B 2576/02 (2013.01)]

49 Claims

1. A method of generating spectroscopy parameters for medical evaluation of a subject, comprising:

obtaining a series of ¹²⁹Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of the subject during a breathing maneuver;

fitting real and imaginary components of the FIDs in a time domain with a curve fitting function modeled with one or more non-Lorentzian line shapes, wherein the curve fitting function models each of a ¹²⁹Xe barrier resonance, a ¹²⁹Xe gas-phase resonance and a ¹²⁹Xe red blood cell (RBC) resonance, with the ¹²⁹Xe barrier resonance modeled, at least in part, with the one or more non-Lorentzian line shapes; and

electronically generating a plurality of ¹²⁹Xe spectral parameters comprising RBC spectral parameters of RBC amplitude, RBC chemical shift (ppm), RBC full width at half maximum (FWHM) (ppm) and RBC phase (degrees) based on the fitting, wherein the plurality of ¹²⁹Xe spectral parameters include static and dynamic ¹²⁹Xe spectral parameters using plots over time of at least one of:

(i) barrier amplitude, barrier chemical shift (ppm), and one or more barrier FWHM (ppm) parameters; and

(ii) the RBC amplitude, the RBC chemical shift (ppm), the RBC FWHM (ppm), and the RBC phase (degrees),

wherein the static and dynamic ¹²⁹Xe spectral parameters comprise RBC amplitude oscillations, RBC chemical shift oscillations, RBC FWHM oscillations and RBC phase oscillations, and

correcting peak-to-peak amplitude of the RBC amplitude oscillations based at least in part on an estimated pulmonary exchange volume of the subject;

wherein the method further comprises diagnosing a medical condition of the subject based on the static and dynamic ¹²⁹Xe spectral parameters.

28. A method of generating spectroscopy parameters, comprising:

providing an inhalable hyperpolarized ¹²⁹Xe gas to a subject;

obtaining, from a Magnetic Resonance Imaging (MRI) scanner, a series of ¹²⁹Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of the subject during a breathing maneuver while the subject is held in a bore of a magnet of the MM scanner;

electronically fitting the FIDs with a curve fitting function modeled with one or more non-Lorentzian line shapes;

electronically generating a plurality of ¹²⁹Xe spectral parameters based on the fitting, wherein the plurality of ¹²⁹Xe spectral parameters include static and/or dynamic ¹²⁹Xe spectral parameters using plots over time of:

(i) barrier amplitude, barrier chemical shift (ppm), and one or more barrier full width at half maximum (FWHM)(ppm) parameters; and

(ii) red blood cell (RBC) amplitude, RBC chemical shift (ppm), RBC FWHM (ppm), and RBC phase (degrees); and

electronically adjusting amplitude “ARBc” of the RBC amplitude plot by multiplying by:

(V_stroke_ref/V_stroke)*(PEV/PEV_ref),

where V stroke ref is a reference stroke volume, V stroke is a subject's actual stroke volume, PEV ref is a reference pulmonary exchange volume, and PEV is the subject's measured pulmonary exchange volume.

29. A computer system for electronic medical evaluation of lungs of a plurality of different subjects, the computer system comprising at least one processor configured to:

obtain a series of ¹²⁹Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of a respective subject during a breathing maneuver;

fit the FIDs with a curve fitting function modeled with one or more non-Lorentzian line shapes;

electronically generate a plurality of ¹²⁹Xe spectral parameters based on the curve fitting, wherein the plurality of ¹²⁹Xe spectral parameters include static and/or dynamic ¹²⁹Xe spectral parameters using plots over time of:

(i) barrier amplitude, barrier chemical shift (ppm), and one or more barrier full width at half maximum (FWHM)(ppm) parameters; and

(ii) red blood cell (RBC) spectral parameters comprising RBC amplitude, RBC chemical shift (ppm), RBC FWHM (ppm), and RBC phase (degrees);

high-pass filter each of the RBC amplitude, RBC chemical shift, RBC phase and RBC FWHM with a 0.5 Hz cutoff frequency to thereby remove residual baseline variation and provide filtered parameter plots of the RBC spectral parameters; and

provide the filtered parameter plots of the RBC spectral parameters to an image processing circuit configured to analyze the filtered parameter plots of the RBC spectral parameters to determine if the respective subject has one or more cardiopulmonary conditions and/or a lung impairment or disease.

32. A method of non-invasively screening a subject for one or more cardiopulmonary conditions, comprising:

obtaining a series of ¹²⁹Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of the subject during a breathing maneuver;

(i) barrier amplitude, barrier chemical shift (ppm), and one or more barrier FWHM (ppm) parameters; and

(ii) the RBC amplitude, the RBC chemical shift (ppm), the RBC FWHM (ppm), and the RBC phase (degrees),

wherein the static and dynamic ¹²⁹Xe spectral parameters comprise RBC amplitude oscillations, RBC chemical shift oscillations, RBC FWHM oscillations and RBC phase oscillations;

obtaining ¹²⁹Xe Magnetic Resonance Imaging (MRI) gas exchange images of the lung or lungs of the subject;

electronically calculating RBC transfer defects, ventilation defects and barrier defects from the ¹²⁹Xe Magnetic Resonance Imaging (MM) gas exchange images of the lung or lungs of the subject and

electronically providing a database comprising a plurality of defined different disease patterns, wherein the plurality of defined disease patterns comprise:

pre-capillary pulmonary hypertension defined at least in part by a respective defined disease pattern comprising peak-to-peak amplitude of RBC amplitude oscillations that is 7.9% or less, and

post-capillary vascular disease defined at least in part by a respective defined disease pattern comprising peak-to-peak amplitude of RBC amplitude oscillations that is greater than 13.85%.

41. A method of generating spectroscopy parameters for medical evaluation of a subject, comprising:

obtaining a series of ¹²⁹Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of the subject during a breathing maneuver;

(i) barrier amplitude, barrier chemical shift (ppm), and one or more barrier FWHM (ppm) parameters; and

(ii) the RBC amplitude, the RBC chemical shift (ppm), the RBC FWHM (ppm), and the RBC phase (degrees),

wherein the static and dynamic ¹²⁹Xe spectral parameters comprise RBC amplitude oscillations, RBC chemical shift oscillations, RBC FWHM oscillations and RBC phase oscillations;

electronically providing a database comprising a plurality of defined different disease patterns of the ¹²⁹Xe spectral parameters correlated to different pulmonary hypertension and/or interstitial lung diseases, wherein at least some of the plurality of defined disease patterns comprise defined sets of one or more features of at least two of the RBC amplitude oscillations, the RBC chemical shift oscillations, the RBC FWHM oscillations and the RBC phase oscillations; and

wherein, when the RBC amplitude oscillations are at least 1.5X larger than a healthy cohort, and when the RBC (chemical shift) oscillations and the RBC phase oscillations are at least 2X above a healthy cohort, identifying that the subject has Idiopathic pulmonary fibrosis (IPF).