Systems and Methods for Assessing Pulmonary Gas Transfer using Hyperpolarized 129XE MRI

Abstract

Methods and systems for assessing pulmonary gas exchange and/or alveolar-capillary barrier status include using spin echo pulse techniques to generate at least one 3-D MRI image of 129 Xe dissolved in the red blood cell (RBC) and barrier compartments in the gas exchange regions of the lungs of a patient.

1 . A method for providing MRI data of pulmonary gas exchange and/or alveolar-capillary barrier status, comprising:
 transmitting an RF MRI excitation pulse imaging sequence configured to excite dissolved phase hyperpolarized  129 Xe in a gas exchange region of a lung of a subject; and   generating a three-dimensional  129 Xe MRI image of a blood-gas barrier of the lung using dissolved phase  129 Xe MRI image signal replenishment data associated with both red blood cell (RBC) compartment and a barrier compartment,   wherein the RF excitation pulse imaging sequence comprises a 3-D spin echo imaging sequence whereby the 3-D spin echo sequence generates an echo at about 90 degrees phase difference between the RBC compartment and the barrier compartment signals.   
   
   
       2 . A method according to  claim 1 , wherein a 180 degree rf refocusing pulse is timed sufficient early and a readout gradient is sufficiently delayed to generate the 90 degree phase difference between the RBC and barrier compartment signals at a center of k-space. 
   
   
       3 . A method according to  claim 1 , wherein the transmitting and generating steps are carried out using under-sampled data acquisition and reconstruction. 
   
   
       4 . A method according to  claim 1 , wherein the generating step comprises:
 obtaining a gas-phase  129 Xe MRI image of the patient;   electronically generating a field map of spatially varying field shifts corresponding to magnetic field inhomogeneity associated with an MRI scanner based on the obtained gas-phase  129 Xe; and   electronically correcting phase of signal data associated with dissolved phase  129 Xe MRI RBC and barrier compartment signals using the generated field-map.   
   
   
       5 . A method according to  claim 1 , wherein the transmitting step has a RF pulse repetition time of between about 10-100 ms, and comprises a large rf flip angle excitation pulse of at least about 40 degrees with a second refocusing rf flip angle pulse, and wherein the generating step is carried out using a single breath hold supply of hyperpolarized  129 Xe in the lung of the subject. 
   
   
       6 . A method according to  claim 5 , wherein the single-breath hold supply of hyperpolarized  129 Xe in the lung has a breath hold duration of about 15 seconds. 
   
   
       7 . A method according to  claim 5 , wherein the RF pulse repetition time is about 40 ms. 
   
   
       8 . A method according to  claim 1 , wherein the three-dimensional image has resolution sufficient to visually indicate regions of impaired lung function. 
   
   
       9 . A method according to  claim 1 , wherein the three-dimensional image has sufficient resolution to visually depict a functional biomarker in patients with radiation fibrosis. 
   
   
       10 . A method according to  claim 1 , wherein the three-dimensional image has sufficient resolution to visually indicate thickening and/or thinning of a blood gas barrier. 
   
   
       11 . A method according to  claim 1 , wherein the three-dimensional image has sufficient resolution to visually indicate a loss in microvasculature or a loss or increase in alveolar surface area. 
   
   
       12 . A method according to  claim 1 , wherein image signal data for the at least one  129 Xe MRI barrier image and the image signal data of the  129 Xe MRI RBC compartment are received substantially concurrently on different receiver channels associated with an MRI scanner, and wherein the RF pulse sequence includes at least one RF pulse repetition time (TR) of between about 10-60 ms. 
   
   
       13 . An MRI scanner system, comprising:
 an MRI scanner comprising an MRI receiver with a plurality of channels including a first channel configured to receive  129 Xe RBC signal data of an RBC compartment of a lung of a patient and a second channel configured to receive  129 Xe barrier compartment signal data of the lung of the patient,   wherein the MRI scanner is configured to programmatically set an MRI scanner frequency and phase to a  129 Xe dissolved phase imaging mode configured for xenon alveolar-capillary transfer imaging.   
   
   
       14 . An MRI scanner according to  claim 13 , wherein the first channel receiver phase is set such that a RBC resonance corresponds to an imaginary channel. 
   
   
       15 . An MRI scanner according to  claim 13 , wherein the second channel receiver phase is set such that a barrier resonance corresponds to a real channel. 
   
   
       16 . An MRI scanner according to  claim 13 , wherein the MRI scanner comprises a scanning sequence that automatically switches the MRI scanner frequency between a tuned frequency for  129 Xe gas to a different tuned frequency for dissolved phase  129 Xe, then back to the frequency for the  129 Xe gas phase to thereby acquire portions of gas and dissolved image data sets in an interleaved manner. 
   
   
       17 . An MRI scanner according to  claim 13 , wherein the MRI scanner is configured to provide a first  129 Xe MRI RBC image of the lung and a second corresponding  129 Xe MRI barrier image of the lung and electronically display the two images substantially concurrently side by side. 
   
   
       18 . An MRI scanner according to  claim 13 , wherein the MRI scanner is configured to programmatically direct the MRI scanner to transmit a 3-D spin echo RF excitation pulse sequence configured to create a 90 degree phase difference between the RBC and barrier signals at a center of k-space. 
   
   
       19 . An MRI scanner according to  claim 18 , wherein the spin echo pulse sequence has a first large flip angle excitation pulse followed by about a 180 degree rf refocusing pulse, the refocusing pulse being timed sufficient early and a readout gradient timed sufficiently delayed to generate the 90 degree phase difference between the RBC and barrier compartment signals at a center of k-space. 
   
   
       20 . A computer program product for generating  129 Xe MRI images, comprising:
 a computer readable storage medium having computer readable program code embodied therein, the computer readable program code comprising:   computer readable program code configured to generate a 3-D spin echo RF excitation pulse sequence configured to create a 90 degree phase difference between dissolved phase hyperpolarized  129 Xe signals in RBC and barrier compartments, respectively, at a center of k-space;   computer readable program code configured to obtain the dissolved phase MRI signal of  129 Xe associated with red blood cells in a gas exchange region of the lung, wherein signal attenuation in the image is associated with reduced alveolar capillary transfer capacity; and   computer readable program code configured to obtain the dissolved phase MRI signal of  129 Xe associated with a alveolar-capillary barrier in the lung; and   computer readable program code configured to generate a 3-D MRI image based on the obtained dissolved phase barrier and RBC signals.