Phase-Resolved Functional Lung (PREFUL) MRI to Quantify Ventilation: Feasibility and Physiological Relevance in Severe Asthma.

RATIONALE AND OBJECTIVES: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease. MATERIALS AND METHODS: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing 1H MRI, 129Xe MRI, spirometry, and oscillometry. A subset of participants (n = 23) performed chest CT and another subset of participants with asthma (n = 19) repeated 1H MRI following the administration of a bronchodilator. VDP was calculated for both PREFUL and 129Xe MRI. Additionally, the percent of functional small airways disease was determined from CT parametric response maps (PRMfSAD). RESULTS: PREFUL VDP measured pre-bronchodilator (19.1% [7.4-43.3], p = 0.0002) and post-bronchodilator (16.9% [6.1-38.4], p = 0.0007) were significantly greater than that of healthy controls (7.5% [3.7-15.5]) and was significantly decreased post-bronchodilator (from 21.9% [10.1-36.9] to 16.9% [6.1-38.4], p = 0.0053). PREFUL VDP was correlated with spirometry (FEV1%pred: r = -0.46, p = 0.0023; FVC%pred: r = -0.35, p = 0.024, FEV1/FVC: r = -0.46, p = 0.0028), 129Xe MRI VDP (r = 0.39, p = 0.013), and metrics of small airway disease (CT PRMfSAD: r = 0.55, p = 0.021; Xrs5 Hz: r = -0.44, p = 0.0046, and AX: r = 0.32, p = 0.044). CONCLUSION: PREFUL-derived VDP is responsive to bronchodilator therapy in asthma and is associated with measures of airflow obstruction and small airway dysfunction. These findings validate PREFUL VDP as a physiologically relevant and accessible ventilation imaging outcome measure in asthma.

Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease.

BACKGROUND: Multiple-breath washout (MBW) 129 Xe MRI (MBW Xe-MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies. PURPOSE: To assess intravisit and intervisit repeatability of MBW Xe-MRI in healthy and CF children. STUDY TYPE: Prospective, longitudinal cohort study. SUBJECTS: A total of 18 pediatric subjects (7 healthy, 11 CF). FIELD STRENGTH/SEQUENCE: A 3 T/2D coronal hyperpolarized (HP) 129 Xe images using GRE sequence. ASSESSMENT: All subjects completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, nitrogen [N2 ] MBW for lung clearance index [LCI]) and ventilation defect percent (VDP) at baseline (visit 1) and 1-month after. Fractional ventilation (FV), coefficient of variation (CoVFV ) maps were calculated from MBW Xe-MRI data acquired between intervening air washout breaths performed after an initial xenon breath-hold. Skewness of FV and CoVFV map distributions was also assessed. STATISTICAL TESTS: Repeatability: intraclass correlation coefficients (ICC), within-subject coefficient of variation (CV%), repeatability coefficient (CR). Agreement: Bland-Altman. For correlations between MBW Xe-MRI, VDP and PFTs: Spearman's correlation. Significance threshold: P < 0.05. RESULTS: For FV, intravisit median [IQR] ICC was high in both healthy (0.94 [0.48, 0.99]) and CF (0.83 [0.04, 0.97]) subjects. CoVFV also had good intravisit ICC in healthy (0.92 [0.42, 0.99]) and CF (0.79 [0.02, 0.96]) subjects. Similarly, for FV, intervisit ICC was high in health (0.94 [0.68, 0.99]) and CF (0.89 [0.61, 0.97]). CoVFV also had good intervisit ICC in health (0.92 [0.42, 0.99]) and CF (0.78 [0.26, 0.94]). FV had better intervisit repeatability than VDP. CoVFV correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline. DATA CONCLUSION: MBW Xe-MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoVFV correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

PURPOSE: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. METHODS: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. RESULTS: Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. CONCLUSION: PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

A 3D stack-of-spirals approach for rapid hyperpolarized 129 Xe ventilation mapping in pediatric cystic fibrosis lung disease.

PURPOSE: To demonstrate the feasibility of a rapid 3D stack-of-spirals (3D-SoS) imaging acquisition for hyperpolarized 129 Xe ventilation mapping in healthy pediatric participants and pediatric cystic fibrosis (CF) participants, in comparison to conventional Cartesian multislice (2D) gradient-recalled echo (GRE) imaging. METHODS: The 2D-GRE and 3D-SoS acquisitions were performed in 13 pediatric participants (5 healthy, 8 CF) during separate breath-holds. Images from both sequences were compared on the basis of ventilation defect percent (VDP) and other measures of image similarity. The nadir of transient oxygen saturation (SpO2 ) decline due to xenon breath-holding was measured with pulse oximetry, and expressed as a percent change relative to baseline. RESULTS: 129 Xe ventilation images were acquired in a breath-hold of 1.2-1.8 s with the 3D-SoS sequence, compared to 6.2-8.8 s for 2D-GRE. Mean ± SD VDP measures for 2D-GRE and 3D-SoS sequences were 5.02 ± 1.06% and 5.28 ± 1.08% in healthy participants, and 18.05 ± 8.26% and 18.75 ± 6.74% in CF participants, respectively. Across all participants, the intraclass correlation coefficient of VDP measures for both sequences was 0.98 (95% confidence interval: 0.94-0.99). The percent change in SpO2 was reduced to -2.1 ± 2.7% from -5.2 ± 3.5% with the shorter 3D-SoS breath-hold. CONCLUSION: Hyperpolarized 129 Xe ventilation imaging with 3D-SoS yielded images approximately five times faster than conventional 2D-GRE, reducing SpO2 desaturation and improving tolerability of the xenon administration. Analysis of VDP and other measures of image similarity demonstrate excellent agreement between images obtained with both sequences. 3D-SoS holds significant potential for reducing the acquisition time of hyperpolarized 129 Xe MRI, and/or increasing spatial resolution while adhering to clinical breath-hold constraints.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

BACKGROUND: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. PURPOSE: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. STUDY TYPE: Prospective. POPULATION: Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3 T. ASSESSMENT: T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. STATISTICAL TEST: Intraclass correlation coefficient (ICC). RESULTS: The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . DATA CONCLUSION: Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3 T scanner, table spine array, and flexible thoracic array) in free-breathing infants. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Evaluating post-bronchodilator response in well-controlled paediatric severe asthma using hyperpolarised 129Xe-MRI: A pilot study.

INTRODUCTION: Pulmonary function tests (PFTs) are the main objective measures used to assess asthma in children. However, PFTs provide a global measure of lung function. Hyperpolarised xenon-129 magnetic resonance imaging (129Xe-MRI) can assess lung function spatially. This cross-sectional cohort study aimed to evaluate the use of 129Xe-MRI in detecting ventilation abnormalities in children with well-controlled severe asthma pre- and post-bronchodilator (BD). METHOD: Six healthy children (aged 11 ± 3) and six with well-controlled severe asthma (14 ± 1) underwent spirometry, multiple breath washout (MBW), and 129Xe-MRI. These tests were repeated post-BD in the asthma cohort. Image analysis was performed in MATLAB. Wilcoxon signed-rank test, repeated measures analysis of variance (ANOVA), and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: A significantly higher number of ventilation defects were found in the asthma cohort pre-BD compared to the healthy participants and post-BD within the asthma cohort (p = 0.02 and 0.01). A greater number of wedge-shaped defects were detected in the asthma cohort pre-BD compared to healthy participants and post-BD within the asthma cohort (p = 0.01 and 0.008, respectively). 129Xe ventilation defect percentage (VDP) and coefficient of variation (CoV) were significantly higher in the asthma cohort pre-BD compared to the healthy cohort (p = 0.006 for both). VDP and CoV were reduced significantly post-BD in the asthma cohort, to a level where there was no longer a significant difference between the two cohorts. CONCLUSION: 129Xe-MRI is a sensitive marker of ventilation inhomogeneity in paediatric severe asthma and may potentially be used as a biomarker to assess disease progression and therapeutic response.

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis.

RATIONALE AND OBJECTIVES: Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). MATERIALS AND METHODS: 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. RESULTS: The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI. CONCLUSION: PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

Smart Bedsheet for Baby Monitoring Application: Measurement and Characterization Results.

This paper describes a research collaboration with Studio 1 Labs to provide the characterization for a novel smart baby monitoring device which includes conductive fabrics. The electrical characterization of the conductive fabrics is important for designing a bedsheet that can adequately be sensitive to physiological movement. Electrical impedance spectroscopy (EIS) has been performed using the Metrohm Autolab potentiostat on a two-fabric interface. For an increase in applied weight, there was an overall decrease in impedance shown both in its real and imaginary components. A simple RC circuit model could be used to describe the system. A test bedsheet was made from a 3x3 conductive fabric matrix stitched into a cotton sheet. Conversely, an increase in resistance was observed from an increase in applied weights at the intersection points of the bedsheet. The following characterization provided useful insight into the future design of the smart bedsheet.

A high-throughput impedimetric platform for cellular analysis: Design, Implementation and Experimental Results.

A high-throughput impedance spectroscopy measurement system was designed and developed for the purpose of biological analysis. This platform consists of a microchip containing a microelectrode array and a multiplexing interface system. Herein we put forward the proposed platform and demonstrate its functionality by performing impedance analysis using N2a cells and its associated medium. The early experimental results demonstrated the high-through impedimetric system to be a strong basis for future modification and development.