Dynamic 129Xe gas exchange spectroscopy

An MRI scanner system, comprising:

• a Magnetic Resonance Imaging (MRI) scanner;
• and
• at least one processor in communication with the MRI scanner and configured to carry out 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.

A medical evaluation system comprising a server in communication with at least one Magnetic Resonance Imaging (MRI) scanner and having at least one processor that carries out 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.

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.

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.

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;
• 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;
• 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;
• 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%.

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;
• 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).

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;
• 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 chemical shift oscillations are more than 5-fold higher than a healthy cohort, and when the RBC phase oscillations are more than 5-fold higher than the healthy cohort, identifying that the subject has Idiopathic pulmonary fibrosis (IPF).

A method of identifying whether a patient has one or more defined medical conditions using 129Xe spectral parameters, comprising:

• obtaining a series of 129Xe free induction decays (FIDs) of a gas exchange region of a lung or lungs of a patient during a breathing maneuver;
• fitting 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 barrier resonance, a red blood cell (RBC) resonance and a gas-phase resonance;
• electronically generating a plurality of static and dynamic 129Xe spectral parameters based on the fitting of a plurality of RBC spectral parameters comprising RBC amplitude, RBC chemical shift (ppm), RBC full width at half maximum (FWHM) (ppm), and RBC phase (degrees), wherein the dynamic 129Xe spectral parameters comprise oscillations of the plurality of the RBC spectral parameters as at least some of the dynamic 129Xe spectral parameters;
• electronically evaluating one or more of a defined shape, pattern, peak size, and/or a frequency of the oscillations of at least two of the RBC amplitude, the RBC chemical shift (ppm), the RBC FWHM (ppm), and the RBC phase (degrees);
• electronically calculating RBC transfer defect percentage, ventilation defect percentage, barrier defect percentage and high barrier uptake percentage using data from 129Xe Magnetic Resonance Imaging (MM) gas exchange images of the lung or lungs of the patient and
• identifying whether the patient has one or more of the defined medical conditions based on the electronic evaluation,
• wherein based at least in part on when peak-to-peak amplitude of the oscillations of the RBC amplitude is 7.9% or less, the patient is identified as likely having pre-capillary pulmonary hypertension, and
• wherein based at least in part on when peak-to-peak amplitude of the oscillations of the RBC amplitude is greater than 10.2% and/or when high barrier uptake percentage is at or above 20%, the patient is identified as likely having Idiopathic pulmonary fibrosis (IPF).