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Troubleshooting and Quality Assurance in Hyperpolarized Xenon Magnetic Resonance Imaging: Tools for High-Quality Image Acquisition

Hyperpolarized (HP) xenon magnetic resonance imaging (129Xe MRI) is a recently federal drug administration (FDA)-approved imaging modality that produces ...

University of Missouri

Chronic obstructive pulmonary disease (COPD) is an irreversible lung disease characterized by small-airway obstruction and alveolar-airspace destruction. Hyperpolarized  Xe diffusion MRI of lung is a promising biomarker for assessing airspace enlargement, but has yet to be validated by direct comparison to lung histology. Here we have compared diffusion measurements of hyperpolarized (HP)  Xe in explanted lungs to regionally matched morphological measures of airspace size.

Direct comparison of  Xe diffusion measurements with quantitative histology in human lungs.

The ventilation defect percent (VDP), measured from hyperpolarized (HP) Xe magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP Xe MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function.

A two-center analysis of hyperpolarized Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker for multi-site trials.

 Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma. We sought to evaluate the effectiveness and safety of using Xe magnetic resonance imaging (Xe MRI) to prioritize the most involved airways for guided BT. Thirty subjects with severe asthma were imaged with volumetric computed tomography and Xe MRI to quantitate segmental ventilation defects. Subjects were randomized to treatment of the six most involved airways in the first session (guided group) or a standard three-session BT (unguided). The primary outcome was the change in Asthma Quality of Life Questionnaire score from baseline to 12 weeks after the first BT for the guided group compared with after three treatments for the unguided group. There was no significant difference in quality of life after one guided compared with three unguided BTs (change in Asthma Quality of Life Questionnaire guided = 0.91 [95% confidence interval, 0.28-1.53]; unguided = 1.49 [95% confidence interval, 0.84-2.14];  = 0.201). After one BT, the guided group had a greater reduction in the percentage of poorly and nonventilated lung from baseline when compared with unguided (-17.2%;  = 0.009). Thirty-three percent experienced asthma exacerbations after one guided BT compared with 73% after three unguided BTs ( = 0.028). Results of this pilot study suggest that similar short-term improvements can be achieved with one BT treatment guided by Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.

Single-Session Bronchial Thermoplasty Guided by Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial.

Adolescent idiopathic scoliosis (AIS) is associated with decreased respiratory quality of life and impaired diaphragm function. Recent hyperpolarized helium (HHe) MRI studies show alveolarization continues throughout adolescence, and mechanical forces are known to impact alveolarization. We therefore hypothesized that patients with AIS would have alterations in alveolar size, alveolar number, or alveolar septal dimensions compared to adolescents without AIS, and that posterior spinal fusion (PSF) might reverse these differences. We conducted a prospective observational trial using HHe MRI to test for changes in alveolar microstructure in control and AIS subjects at baseline and one year. After obtaining written informed consent from subjects' legal guardians and assent from the subjects, we performed HHe and proton MRI in 14 AIS and 16 control subjects aged 8-21 years. The mean age of control subjects (12.9 years) was significantly less than AIS (14.9 years, p = 0.003). At baseline, there were no significant differences in alveolar size, number, or alveolar duct morphometry between AIS and control subjects or between the concave (compressed) and convex (expanded) lungs of AIS subjects. At one year after PSF AIS subjects had an increase in alveolar density in the formerly convex lung (p = 0.05), likely reflecting a change in thoracic anatomy, but there were no other significant changes in lung microstructure. Modeling of alveolar size over time demonstrated similar rates of alveolar growth in control and AIS subjects in both right and left lungs pre- and post-PSF. Although this study suffered from poor age-matching, we found no evidence that AIS or PSF impacts lung microstructure. Trial registration: Clinical trial registration number NCT03539770.

Lung microstructure in adolescent idiopathic scoliosis before and after posterior spinal fusion.

Alveolar development and lung parenchymal simplification are not well characterized in vivo in neonatal patients with respiratory morbidities, such as bronchopulmonary dysplasia (BPD). Hyperpolarized (HP) gas diffusion magnetic resonance imaging (MRI) is a sensitive, safe, nonionizing, and noninvasive biomarker for measuring airspace size in vivo but has not yet been implemented in young infants.

Alveolar Airspace Size in Healthy and Diseased Infant Lungs Measured via Hyperpolarized 3He Gas Diffusion Magnetic Resonance Imaging.

In this study, we compared hyperpolarized He and Xe images from patients with cystic fibrosis using two commonly applied magnetic resonance sequences, standard gradient echo (GRE) and balanced steady-state free precession (TrueFISP) to quantify regional similarities and differences in signal distribution and defect analysis.

Comparison of Hyperpolarized He and Xe MR Imaging in Cystic Fibrosis Patients.

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. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.

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

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. To promote uniformity and adoption of HP  Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the  Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP  Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for  Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP  Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP  Xe MRI for multi-site pulmonary research.

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  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. This method uses a radial one-point Dixon approach to sample dissolved  Xe signal, which is interleaved with a 3D spiral ("FLORET") encoding pattern for gaseous  Xe. Thus, ventilation images are obtained at higher nominal spatial resolution (4.2 × 4.2 × 4.2 mm ) compared with gas-exchange images (6.25 × 6.25 × 6.25 mm ), both competitive with current standards within the Xe-MRI field. Moreover, the short 10 s Xe-MRI acquisition time allows for  H "anatomic" images used for thoracic cavity masking to be acquired within the same breath-hold for a total scan time of about 14 s. Images were acquired using this single-breath method in 11 volunteers (N = 4 healthy, N = 7 post-acute COVID). For 11 of these participants, a separate breath-hold was used to acquire a "dedicated" ventilation scan and five had an additional "dedicated" gas exchange scan. The images acquired using the single-breath protocol were compared with those from dedicated scans using Bland-Altman analysis, intraclass correlation (ICC), structural similarity, peak signal-to-noise ratio, Dice coefficients, and average distance. Imaging markers from the single-breath protocol showed high correlation with dedicated scans (ventilation defect percent, ICC = 0.77, p = 0.01; membrane/gas, ICC = 0.97, p = 0.001; red blood cell/gas, ICC = 0.99, p < 0.001). Images showed good qualitative and quantitative regional agreement. This single-breath protocol enables the collection of essential Xe-MRI information within one breath-hold, simplifying scanning sessions and reducing costs associated with Xe-MRI.

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

The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (Tc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients.

Robert Thomen

Chemical and Biomedical Engineering,
Radiology,
School of Medicine,
Radiology, School of Medicine

University of Missouri

Troubleshooting and Quality Assurance in Hyperpolarized Xenon Magnetic Resonance Imaging: Tools for High-Quality Image Acquisition

Robert Thomen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Chemical and Biomedical Engineering,Radiology,School of Medicine,Radiology, School of Medicine

University of Missouri

Troubleshooting and Quality Assurance in Hyperpolarized Xenon Magnetic Resonance Imaging: Tools for High-Quality Image Acquisition

Chemical and Biomedical Engineering,
Radiology,
School of Medicine,
Radiology, School of Medicine