Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: With improved neonatal care and increased survival of very preterm infants, the incidence of bronchopulmonary dysplasia (BPD, or chronic lung disease of prematurity) has increased.

Goal(s): To evaluate Xe gas-exchange MRI by investigating success rates, sensitivity, and correlations with clinical demographics and pulmonary function testing.

Approach: In 24 patients, Xe ventilation, restricted diffusion, and gas-exchange MRI were collected along with pulmonary function testing and electronic health records.

Results: We found hyperpolarized Xe-MRI detects ventilation, lung microstructure, and gas-exchange abnormalities in 53%, 59%, and 82% of patients, respectively. Additionally, ventilation obstruction worsened with age, and two imaging phenotypes were detected.

Impact: Hyperpolarized Xe-MRI detected significant ventilation defects in 53% and lung microstructure abnormalities in 59% of bronchopulmonary dysplasia patients. Gas-exchange MRI revealed two phenotypes, with abnormalities in membrane-uptake (82%), RBC-transfer (65%), and RBC:Membrane ratio (29%).

Keywords: Hyperpolarized MR (Gas), Lung, Denoise, 129Xe MRI

Motivation: Hyperpolarized ¹²⁹Xe (HXe) MRI is a powerful, FDA-approved modality to assess lung function. While improvements in ¹²⁹Xe technology enable polarizations of ~50%, low SNR images still hinder image interpretation and quantification. With only modest improvements in polarization levels still possible, other means must be developed to improve HXe SNR.

Goal(s): Developed a denoising method to improve HXe SNR.

Approach: This study adapts Noise2Void (N2V) denoising for HXe imaging and evaluates its performance on ventilation, diffusion, and gas exchange images.

Results: Comparison with Block Matching 3D indicates the effectiveness of N2V in reducing noise and enhancing image quality. 

Impact: Elevated noise levels in hyperpolarized ¹²⁹Xe MR images lower image quality and quantitative accuracy and are a confounding factor for clinical interpretation. The objective of this work is to develop a ¹²⁹Xe-MR image denoising technique based on unsupervised deep learning.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), asthma, gas-exchange, MRS, lung

Motivation: ¹²⁹Xe MRS quantifies pulmonary gas-exchange by probing inhaled ¹²⁹Xe transfer from the alveolar-membrane to the red-blood-cells (RBC). Recent work suggested a vascular response to asthma therapy, quantifiable using ¹²⁹Xe MRS. 

Goal(s): We aimed to examine if ¹²⁹Xe MRS measurements were predictive of significant 6-week response to ICS/LAMA/LABA in moderate asthma patients.

Approach: ¹²⁹Xe MRS and pulmonary function measurements were acquired prior to and following 6-weeks of therapy.

Results: ¹²⁹Xe RBC:membrane, measured prior to treatment, was predictive of response to ICS/LAMA/LABA at 6 weeks, measured using the fraction-of-exhaled nitric-oxide and the ratio of forced-expiratory-volume in 1-second to forced-vital-capacity. 

Impact: For the first time, ¹²⁹Xe MRS RBC:membrane has been shown to predict early (6-week) response to ICS/LAMA/LABA in moderate asthma. ¹²⁹Xe MRS uncovered a novel pathophysiology in asthma patients, with potential for consideration as a new treatable target. 

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), Lung, Asthma, Spectroscopy

Motivation: Airways disease in asthma is characterized by airway wall thickening, luminal obstruction and smooth muscle hyper-responsiveness. Abnormal CT pulmonary vascular pruning has also been reported. We wondered if ¹²⁹Xe MRS could identify functional abnormalities related to the pulmonary vascular tree, via the measurement of gas-exchange across the alveolar-capillary membranes, into the red-blood-cells.

Goal(s): Measure and compare ¹²⁹Xe MRS RBC:membrane in healthy volunteers, and patients with moderate or severe asthma.

Approach: ¹²⁹Xe MRI, MRS and pulmonary function measures were acquired in healthy-volunteers and asthma participants.

Results: ¹²⁹Xe MR RBC:membrane was significantly different in healthy-volunteers, moderate and severe asthma.

Impact: To our knowledge, this is the first demonstration of significantly different ¹²⁹Xe MRS RBC:membrane values in healthy volunteers, and patients with moderate or severe asthma. Abnormal pulmonary gas-exchange may play a role in asthma, regardless of disease-severity.

Keywords: Hyperpolarized MR (Gas), Lung, Radiation induced lung injury, Modelling

Motivation: Regional assessment of functional decline due to radiation-induced lung injury (RILI) remains challenging

Goal(s): We aimed to assess the accuracy of the recently introduced kinetic model of xenon exchange (kMXE) by comparison with the established MOXE model using hyperpolarised ¹²⁹Xe MRI

Approach: Employing a RILI rat model, we implemented gas exchange mapping of hyperpolarised ¹²⁹Xe MRI chemical shift imaging data using 1D compartmental diffusion models.

Results: The kMXE results matched the MOXE model well. Both models demonstrated asymmetric outcomes in the RILI cohort, diverging from the homogeneous results in the healthy group.

Impact: Using hyperpolarised ¹²⁹Xe MRI, we evaluated the effectiveness of kMXE and MOXE models and demonstrate their ability to uncover regional functional variations, providing potential biomarkers for assessing the longitudinal progression of radiation-induced lung injury.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Keyhole-based ¹²⁹Xe MR imaging of cardiopulmonary oscillations is a promising technique, but repeatability has not been studied. 

Goal(s): To evaluate the repeatability of RBC oscillation amplitude metrics derived from ¹²⁹Xe MRI across multiple time points and correlate these with dynamic spectroscopy measurements.

Approach: A cohort of 21 participants underwent ¹²⁹Xe gas exchange MRI and MRS scans using consortium protocols. Repeatability was assessed using Bland-Altman analysis, with Spearman correlation for cross-modality comparison

Results: The study found repeatability to be high for mean oscillation amplitude but moderate for the binning-derived metrics. Image-derived mean oscillation amplitude correlated strongly to that derived from MRS.

Impact: Analysis of 129Xe MRI cardiopulmonary oscillation metrics show moderate repeatability across same-session scans.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), Transmit Gain Calibration, Bloch-Siegert Shift

Motivation: Transmit gain calibration is necessary for nonproton hyperpolarized MRI to accurately calibrate excitation angles.

Goal(s): To implement a phase-based TG calibration method using the Bloch-Siegert shift for nonproton HP MRI on a preclinical 7T scanner.

Approach: An off-resonance Fermi-shaped Bloch-Siegert pulse follows directly an excitation pulse. Percent difference between our measured Bloch-Siegert TG calibration factors and the validation TG calibration factors for ¹H and ¹³C were calculated.  

Results: Our method allows for fast, accurate, and robust TG calibration of preclinical nonproton HP MRI studies  with minimal error (<5%) for ¹H and ¹³C.

Impact: This method will facilitate efficient transmit calibration for ¹³C and HP ¹²⁹Xe MRI on a preclinical 7T scanner, where limited bore size and the inability to easily implement a thermal calibration phantom can make ¹²⁹Xe TG calibration a challenge.

Keywords: Hyperpolarized MR (Gas), COVID-19, Xenon, Blood

Motivation: We sought to demonstrate the safety and efficacy of a hyperpolarized gas MRI protocol for assessing the pulmonary physiology of long-COVID.

Goal(s): Our goal was to gather preliminary dissolved phase images utilizing unenriched xenon.

Approach: Volumes of 300mL and 500mL of unenriched xenon were hyperpolarized using a 180W diode laser at 795nm and administered to two healthy subjects. Scans were obtained using a 3T SIGNATM Premier scanner and a 129Xe Quadrature T/R lung coil. Images were masked using signal-to-noise thresholding on tissue/plasma signal.

Results: We found strong red blood cell and tissue/plasma xenon signal in both subjects utilizing 300mL of unenriched xenon.

Impact: At present time, successful dissolved xenon imaging has only been described with the use of enriched xenon-129. Our findings suggest that less expensive and more widely available unenriched xenon may be used in dissolved gas MRI.

Keywords: Spectroscopy, Non-Proton, odium, transmembrane transport

Motivation: Transmembrane transport of sodium ions is directly related to the cell functions and metabolisms and could be an indicator of various diseases such as neurodevelopmental disorders, neuropathic pain, etc. There  is a lack of non-invasive and clinically-adaptable techniques for quantifying the rate of transmembrane transport of sodium ions.

Goal(s): Determine the rate of sodium transmembrane transport using noninvasive nuclear magnetic resonance methods.

Approach: ²³Na relaxation exchange spectroscopy (REXSY) was applied to the cellular systems for quantitative analysis. 

Results: The ²³Na REXSY method successfully determined the sub-second transmembrane exchange rate of sodium ions in yeast and HeLa cells.

Impact: Measuring transmembrane rate of sodium via NMR can assist the pathological studies of diseases related to malfunctions of sodium ion channels and/or sodium metabolism. ²³Na REXSY could be coupled to MR imaging to offer novel parameters for clinical diagnosis.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Quantitative ¹²⁹Xe gas exchange MRI, conducted across different imaging centers and scanner platforms, requires consistent healthy reference distributions.

Goal(s): To establish standardized reference values from an 18-30yr old multicenter healthy cohort for ¹²⁹Xe gas exchange MRI.

Approach: Participants from three research centers underwent pulmonary function tests and a standardized ¹²⁹Xe MRI/MRS protocol. Data were processed centrally and corrected for T2*.

Results: A balanced multicenter dataset revealed minimal variability between combined and site-specific reference distributions, validating the combined values for cross-center use. The distribution for 208-ppm excitation could be reliably transformed for 218-ppm excitation.

Impact: This study provides robust cross-platform reference distributions for ¹²⁹Xe gas exchange MRI, facilitating comparison of quantitative imaging in multi-center respiratory research.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), Asthma, Machine learning, Texture analysis

Motivation: ¹²⁹Xe MRI ventilation texture features provide a way to generate quantitative spatial information about ventilation heterogeneity beyond ventilation defect percent, which is important in some asthma patients with patchy (and not obviously segmental or subsegmental) ventilation abnormalities.  

Goal(s): Machine-learning and ¹²⁹Xe MRI ventilation texture-analysis were used to generate ventilation-imaging based models for predicting ICS/LAMA/LABA response. 

Approach: Machine-learning models trained on clinical measurements were compared with those trained on ventilation texture features. 

Results: MRI texture-based models outperformed clinical models for predicting 6-week response. The neighbourhood gray-tone difference matrix strength was the top-ranking texture feature, which significantly correlated with clinical measurements. 

Impact: ¹²⁹Xe MRI ventilation texture features provided unique information about ventilation abnormalities and ventilation patchiness; when texture features were embedded in predictive models, these features outperformed clinical models explaining response to ICS/LAMA/LABA in moderate asthma.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Pulmonary embolism (PE) is a leading cause of cardiovascular death. Timely diagnosis is crucial but challenging. Increasing inspired oxygen levels to 40% or above has proven an effective treatment in acute PE by altering pulmonary gas exchange.

Goal(s): Our goal is to determine if hyperpolarized 129-xenon gas can diagnose PE.

Approach: Hyperpolarized 129-xenon dissolved-phase imaging was evaluated by applying a hyperoxic challenge in a porcine PE model.

Results: Whole lung assessment of dissolved-phase imaging indicates regional pulmonary gas exchange increases with higher inhaled oxygen levels. Nevertheless, hyperoxic challenge effects did not diagnose PE.

Impact: The study shows great potential of a pulmonary gas exchange imaging with the application of dissolved-phase hyperpolarized ¹²⁹Xe imaging throughout a hyperoxic challenge. Nevertheless, the method did not improve diagnosis of pulmonary embolism in our porcine animal model.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), xenon-129, HyperCEST, chemical exchange, Noria, R3-Noria-methanesulfonate

Motivation: In the setting of molecular MRI, designing a contrast agent that can be applied in clinical studies and which offers high sensitivity poses a significant challenge. 

Goal(s): We aimed to demonstrate a novel water-soluble R3-Noria-MeSO₃H macrocycle as a viable supramolecular cage agent for ¹²⁹Xe molecular imaging.

Approach: Hyperpolarized ¹²⁹Xe chemical exchange saturation transfer MR imaging and spectroscopy were conducted in vitro using a 3.0T clinical MRI scanner. 

Results: We demonstrated that R3-Noria-MeSO₃H produces a superior HyperCEST effect and investigated its dependence on concentrations in various aqueous solutions.

Impact: The introduction of the novel R3-Noria-MeSO₃H macrocycle for HP ¹²⁹Xe HyperCEST imaging marks a critical milestone, establishing a new frontier in ¹²⁹Xe molecular imaging with heightened sensitivity and potential for advancing clinical applications in diagnostic precision and therapeutic monitoring.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Hyperpolarized ¹²⁹Xe MRI, pivotal for lung function analysis, faces challenges in standardizing ventilation distribution calculations, particularly regarding image rescaling and major airway inclusion.

Goal(s): To develop a deep learning-based method to segment the trachea and assess its impact on the ventilation distribution.

Approach: We trained and compared various deep learning models for robust segmentation. 

Results: In patients with interstitial lung disease, the ratio of ¹²⁹Xe signal in the trachea versus the distal lung is 2.5-fold higher than in healthy volunteers. If such signal is not segmented out before histogram rescaling, ventilation distributions may be substantially skewed in patients with restrictive disease.

Impact: This research paves the way for redefining the calculation of ventilation distribution in pulmonary imaging by incorporating large airways like the trachea, potentially leading to more precise imaging metrics and improved clinical outcomes for pulmonary diseases.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas), hyper-CEST, New Devices

Motivation: Routine measurements of hyperpolarized media utilizing low-cost benchtop-NMR spectrometers should allow for sensitive bio-chemical analysis. So far, just an elaborate handling of hyperpolarized ¹²⁹Xe was demonstrated.

Goal(s): To deliver highly polarized ¹²⁹Xe to the sample at the time of demand within the NMR spectrometer.

Approach: We present the combination of a continuous-flow ¹²⁹Xe polarizer with a commercial benchtop-NMR spectrometer. The gas flow into the NMR sample is time-controlled by the spectrometer pulse program and xenon gas densities are user adjustable.

Results: In routine experimentation polarization transfer-losses were minimized, thus allowing for e.g.,  characterization and concentration determination of future contrast agents.

Impact: Our work demonstrates day-to-day measurements utilizing well-established flow-through 129Xe polarizers in combination with low-cost benchtop NMR spectrometers yielding high sensitivity. Thus, utilizing the high affinity of xenon to proteins or cage molecules allows for various biological studies alike concentration determination.

Keywords: Hyperpolarized MR (Gas), Hyperpolarized MR (Gas)

Motivation: Chemical shift saturation recovery (CSSR) MR spectroscopy using hyperpolarized xenon-129 (HXe) is sensitive to abnormal lung function but lacks regionality.

Goal(s): Add regional information to CSSR MR spectroscopy with variable echo time (TE) chemical shift imaging (CSI).

Approach: Comparison of CSI-CSSR to global CSSR measurements in the lungs of a healthy and an irradiated rat.

Results: CSI-CSSR yields results comparable to whole-lung CSSR spectroscopy but with added regionality.

Impact: CSI-CSSR allows the regional quantification of apparent alveolar septal wall thickness, T2*, and resonance frequency shifts. This approach greatly enhances the sensitivity for the detection of abnormal xenon gas-exchange processes in heterogeneous lung disease.