Quantifying spatial and dynamic lung abnormalities with 3D PREFUL FLORET UTE imaging: A feasibility study.

Purpose: Pulmonary MRI faces challenges due to low proton density, rapid transverse magnetization decay, and cardiac and respiratory motion. The fermat-looped orthogonally encoded trajectories (FLORET) sequence addresses these issues with high sampling efficiency, strong signal, and motion robustness, but has not yet been applied to phase-resolved functional lung (PREFUL) MRI-a contrast-free method for assessing pulmonary ventilation during free breathing. This study aims to develop a reconstruction pipeline for FLORET UTE, enhancing spatial resolution for three-dimensional (3D) PREFUL ventilation analysis.

A thermally polarized, dissolved-phase Xe phantom for quality-control and multisite comparisons of gas-exchange imaging.

Harmonizing and validating Xe gas exchange imaging across multiple sites is hampered by a lack of a quantitative standard that 1) displays the unique spectral properties of Xe observed from human subjects in vivo and 2) has short enough T times to enable practical imaging. This work describes and demonstrates the development of two dissolved-phase, thermally polarized phantoms that mimic the in-vivo, red blood cell and membrane resonances of Xe dissolved in human lungs. Following optimization, combinations of two common organic solvents, acetone and dimethyl sulfoxide, resulted in two in-vivo-like dissolved-phase Xe phantoms yielding chemical shifts of 212.

Xe Image Processing Pipeline: An open-source, graphical user interface application for the analysis of hyperpolarized Xe MRI.

Purpose: Hyperpolarized Xe MRI presents opportunities to assess regional pulmonary microstructure and function. Ongoing advancements in hardware, sequences, and image processing have helped it become increasingly adopted for both research and clinical use. As the number of applications and users increase, standardization becomes crucial.

Same-Day Repeatability and 28-Day Reproducibility of Xenon MRI Ventilation in Children With Cystic Fibrosis in a Multi-Site Trial.

Background: MRI with xenon-129 gas (Xe MRI) can assess airflow obstruction and heterogeneity in lung diseases. Specifically, Xe MRI may represent a sensitive modality for future therapeutic trials of cystic fibrosis (CF) therapies. The reproducibility of Xe MRI has not yet been assessed in the context of a multi-site study.

High-quality FLORET UTE imaging for clinical translation.

Purpose: To develop a robust 3D ultrashort-TE (UTE) protocol that can reproducibly provide high-quality images, assessed by the ability to yield clinically diagnostic images, and is suitable for clinical translation.

Theory And Methods: Building on previous work, a UTE sampled with Fermat looped orthogonally encoded trajectories (FLORET) was chosen as a starting point due to its shorter, clinically reasonable scan times. Modifications to previous FLORET implementations included gradient waveform frequency limitations, a new trajectory ordering scheme, a balanced SSFP implementation, fast gradient spoiling, and full inline reconstruction.

Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarized Xe diffusion MRI.

Rationale: Cystic Fibrosis (CF) progresses through recurrent infection and inflammation, causing permanent lung function loss and airway remodeling. CT scans reveal abnormally low-density lung parenchyma in CF, but its microstructural nature remains insufficiently explored due to clinical CT limitations. To this end, diffusion-weighted Xe MRI is a non-invasive and validated measure of lung microstructure.

A decay-modeled compressed sensing reconstruction approach for non-Cartesian hyperpolarized Xe MRI.

Purpose: Hyperpolarized Xe MRI benefits from non-Cartesian acquisitions that sample k-space efficiently and rapidly. However, their reconstructions are complex and burdened by decay processes unique to hyperpolarized gas. Currently used gridded reconstructions are prone to artifacts caused by magnetization decay and are ill-suited for undersampling.

Analytical corrections for B-inhomogeneity and signal decay in multi-slice 2D spiral hyperpolarized Xe MRI using keyhole reconstruction.

Purpose: Hyperpolarized xenon MRI suffers from heterogeneous coil bias and magnetization decay that obscure pulmonary abnormalities. Non-physiological signal variability can be mitigated by measuring and mapping the nominal flip angle, and by rescaling the images to correct for signal bias and decay. While flip angle maps can be calculated from sequentially acquired images, scan time and breath-hold duration are doubled.

Initial feasibility and challenges of hyperpolarized Xe MRI in neonates with bronchopulmonary dysplasia.

Purpose: The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized Xe MRI in neonates with BPD.

B and magnetization decay correction for hyperpolarized Xe lung imaging using sequential 2D spiral acquisitions.

Purpose: To mitigate signal variations caused by inhomogeneous RF and magnetization decay in hyperpolarized Xe ventilation images using flip-angle maps generated from sequential 2D spiral ventilation images acquired in a breath-hold. Images and correction maps were compared with those obtained using conventional, 2D gradient-recalled echo.

Theory And Methods: Analytical expressions to predict signal intensity and uncertainty in flip-angle measurements were derived from the Bloch equations and validated by simulations and phantom experiments.

A single-breath-hold protocol for hyperpolarized Xe ventilation and gas exchange imaging.

Hyperpolarized Xe MRI (Xe-MRI) is increasingly used to image the structure and function of the lungs. Because Xe imaging can provide multiple contrasts (ventilation, alveolar airspace size, and gas exchange), imaging often occurs over several breath-holds, which increases the time, expense, and patient burden of scans. We propose an imaging sequence that can be used to acquire Xe-MRI gas exchange and high-quality ventilation images within a single, approximately 10 s, breath-hold.

Short-term structural and functional changes after airway clearance therapy in cystic fibrosis.

Background: Airway clearance therapy (ACT) with a high-frequency chest wall oscillation (HFCWO) vest is a common but time-consuming treatment. Its benefit to quality of life for cystic fibrosis (CF) patients is well established but has been questioned recently as new highly-effective modulator therapies begin to change the treatment landscape. Xe ventilation MRI has been shown to be very sensitive to lung obstruction in mild CF disease, making it an ideal tool to identify and quantify subtle, regional changes.

Childhood to adulthood: Accounting for age dependence in healthy-reference distributions in Xe gas-exchange MRI.

Purpose: Xenon-129 ( Xe) gas-exchange MRI is a pulmonary-imaging technique that provides quantitative metrics for lung structure and function and is often compared to pulmonary-function tests. Unlike such tests, it does not normalize to predictive values based on demographic variables such as age. Many sites have alluded to an age dependence in gas-exchange metrics; however, a procedure for normalizing metrics has not yet been introduced.

Diffusion weighted hyperpolarized Xe MRI of the lung with 2D and 3D (FLORET) spiral.

Purpose: To enable efficient hyperpolarized Xe diffusion imaging using 2D and 3D (Fermat Looped, ORthogonally Encoded Trajectories, FLORET) spiral sequences and demonstrate that Xe ADCs obtained using these sequences are comparable to those obtained using a conventional, 2D gradient-recalled echo (GRE) sequence.

Theory And Methods: Diffusion-weighted Xe MRI (b-values = 0, 7.5, 15 s/cm ) was performed in four healthy volunteers and one subject with lymphangioleiomyomatosis using slice-selective 2D-GRE (scan time = 15 s), slice-selective 2D-Spiral (4 s), and 3D-FLORET (16 s) sequences.

Pediatric Xe Gas-Transfer MRI-Feasibility and Applicability.

Background: Xe gas-transfer MRI provides regional measures of pulmonary gas exchange in adults and separates xenon in interstitial lung tissue/plasma (barrier) from xenon in red blood cells (RBCs). The technique has yet to be demonstrated in pediatric populations or conditions.

Purpose/hypothesis: To perform an exploratory analysis of Xe gas-transfer MRI in children.

Improving hyperpolarized Xe ADC mapping in pediatric and adult lungs with uncertainty propagation.

Rationale: Hyperpolarized (HP) Xe-MRI provides non-invasive methods to quantify lung function and structure, with the Xe apparent diffusion coefficient (ADC) being a well validated measure of alveolar airspace size. However, the experimental factors that impact the precision and accuracy of HP Xe ADC measurements have not been rigorously investigated. Here, we introduce an analytical model to predict the experimental uncertainty of Xe ADC estimates.

Protocols for multi-site trials using hyperpolarized Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the Xe MRI clinical trials consortium.

Hyperpolarized (HP) Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies.

Human upper-airway respiratory airflow: In vivo comparison of computational fluid dynamics simulations and hyperpolarized 129Xe phase contrast MRI velocimetry.

Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard.

Hyperpolarized Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases.

Rationale: There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding.