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Infants admitted to the neonatal intensive care unit (NICU) often suffer from multifaceted pulmonary morbidities that are not well understood. Ultrashort echo time (UTE) magnetic resonance imaging (MRI) is a promising technique for pulmonary imaging in this population without requiring exposure to ionizing radiation. The aims of this study were to investigate the effect of neonatal pulmonary disease on R2* and tissue density and to utilize numerical simulations to evaluate the effect of different alveolar structures on predicted R2*.This was a prospective study, in which 17 neonatal human subjects (five control, seven with bronchopulmonary dysplasia [BPD], five with congenital diaphragmatic hernia [CDH]) were enrolled. Twelve subjects were male and five were female, with postmenstrual age (PMA) at MRI of 39.7 ± 4.7 weeks. A 1.5T/multiecho three‐dimensional UTE MRI was used. Pulmonary R2* and tissue density were compared across disease groups over the whole lung and regionally. A spherical shell alveolar model was used to predict the expected R2* over a range of tissue densities and tissue susceptibilities. Tests for significantly different mean R2* and tissue densities across disease groups were evaluated using analysis of variance, with subsequent pairwise group comparisons performed using t tests. Lung tissue density was lower in the ipsilateral lung in CDH compared to both controls and BPD patients (both p < 0.05), while only the contralateral lung in CDH (CDHc) had higher whole‐lung R2* than both controls and BPD (both p < 0.05). R2* differences were significant between controls and CDHc within all tissue density ranges (all p < 0.05) with the exception of the 80%–90% range (p = 0.17). Simulations predicted an inverse relationship between alveolar tissue density and R2* that matches empirical human data. Alveolar wall thickness had no effect on R2* independent of density (p = 1). The inverse relationship between R2* and tissue density is influenced by the presence of disease globally and regionally in neonates with BPD and CDH in the NICU. Level of Evidence: 2. Technical Efficacy Stage: 2. [ABSTRACT FROM AUTHOR]

Purpose: The MR properties (chemical shifts and R2∗ decay rates) of dissolved‐phase hyperpolarized (HP) 129Xe are confounded by the large magnetic field inhomogeneity present in the lung. This work improves measurements of these properties using a model‐based image reconstruction to characterize the R2∗ decay rates of dissolved‐phase HP 129Xe in healthy subjects and patients with idiopathic pulmonary fibrosis (IPF). Methods: Whole‐lung MRS and 3D radial MRI with four gradient echoes were performed after inhalation of HP 129Xe in healthy subjects and patients with IPF. A model‐based image reconstruction formulated as a regularized optimization problem was solved iteratively to measure regional signal intensity in the gas, barrier, and red blood cell (RBC) compartments, while simultaneously measuring their chemical shifts and R2∗ decay rates. Results: The estimation of spectral properties reduced artifacts in images of HP 129Xe in the gas, barrier, and RBC compartments and improved image SNR by over 20%. R2∗ decay rates of the RBC and barrier compartments were lower in patients with IPF compared to healthy subjects (P < 0.001 and P = 0.005, respectively) and correlated to DLCO (R = 0.71 and 0.64, respectively). Chemical shift of the RBC component measured with whole‐lung spectroscopy was significantly different between IPF and normal subjects (P = 0.022). Conclusion: Estimates for R2∗ in both barrier and RBC dissolved‐phase HP 129Xe compartments using a regional signal model improved image quality for dissolved‐phase images and provided additional biomarkers of lung injury in IPF. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: This work quantified alveolar airspace size via HP gas diffusion MRI in healthy and diseased explanted infant lung specimens, with comparison to histological morphometry. Methods: Lung specimens from 8 infants were obtained: 7 healthy left upper lobes (0–16 months, post-autopsy) and 1 left lung with filamin-A mutation, closely representing BPD lung disease (11 months, post-transplantation). Specimens were imaged using HP 3He diffusion MRI to generate apparent diffusion coefficients (ADCs) as biomarkers of alveolar airspace size, with comparison to mean linear intercept (Lm) via quantitative histology. Results: Mean ADC and Lm were significantly increased throughout the diseased specimen (ADC = 0.26 ± 0.06 cm2/s, Lm = 587 ± 212 µm) compared with healthy specimens (ADC = 0.14 ± 0.03 cm2/s, Lm = 133 ± 37 µm; p < 1 × 10−7); increased values reflect enlarged airspaces. Mean ADCs in healthy specimens were significantly correlated to Lm (r = 0.69, p = 0.041). Conclusions: HP gas diffusion MRI is sensitive to healthy and diseased regional alveolar airspace size in infant lungs, with good comparison to quantitative histology in ex vivo specimens. This work demonstrates the translational potential of gas MRI techniques for in vivo assessment of normal and abnormal alveolar development in neonates with pulmonary disease. [ABSTRACT FROM AUTHOR]

Purpose: Novel demonstration of R2∗ and tissue density estimation in infant lungs using 3D ultrashort echo time MRI. Differences between adult and neonates with no clinical indication of lung pathology is explored, as well as relationships between parameter estimates and gravitationally dependent position and lung inflation state. This provides a tool for probing physiologic processes that may be relevant to pulmonary disease and progression in newborns. Methods: R2∗ and tissue density were estimated in a phantom consisting of standards allowing for ground truth comparisons and in human subjects (N = 5 infants, N = 4 adults, no clinical indication of lung dysfunction) using a 3D radial multiecho ultrashort echo time MRI sequence. Whole lung averages were compared between infants and adults. Dependence of the metrics on anterior‐posterior position as well as between end‐tidal inspiration and expiration were explored, in addition to the general relationship between R2∗ and tissue density. Results: Estimates in the phantom did not differ significantly from ground truth. Neonates had significantly lower mean R2∗ (P =.006) and higher mean tissue density (P = 1.5e‐5) than adults. Tissue density and R2∗ were both significantly dependent on anterior‐posterior position and lung inflation state (P <.005). An overall inverse relationship was found between R2∗ and tissue density, which was similar in both neonates and adults. Conclusion: Estimation of tissue density and R2∗ in free breathing, nonsedated, neonatal patients is feasible using multiecho ultrashort echo time MRI. R2∗ was no different between infants and adults when matched for tissue density, although density of lung parenchyma was, on average, lower in adults than neonates. [ABSTRACT FROM AUTHOR]

Background: MRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.Purpose: To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase 129 Xe imaging and their dependence on intervisit changes in lung inflation volume.Study Type: Prospective.Population: Fourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9).Field Strength: 1.5T.Assessment: Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs).Statistical Tests: Repeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression.Results: Mean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DLCO (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found.Data Conclusion: Three commonly used 129 Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DLCO .Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190. [ABSTRACT FROM AUTHOR]

Background: Neonatal dynamic tracheal collapse (tracheomalacia, TM) is a common and serious comorbidity in infants, particularly those with chronic lung disease of prematurity (bronchopulmonary dysplasia, BPD) or congenital airway or lung-related conditions such as congenital diaphragmatic hernia (CDH), but the underlying pathology, impact on clinical outcomes, and response to therapy are not well understood. There is a pressing clinical need for an accurate, objective, and safe assessment of neonatal TM.Purpose: To use retrospectively respiratory-gated ultrashort echo-time (UTE) MRI to noninvasively analyze moving tracheal anatomy for regional, quantitative evaluation of dynamic airway collapse in quiet-breathing, nonsedated neonates.Study Type: Prospective.Population/subjects: Twenty-seven neonatal subjects with varying respiratory morbidities (control, BPD, CDH, abnormal polysomnogram).Field Strength/sequence: High-resolution 3D radial UTE MRI (0.7 mm isotropic) on 1.5T scanner sited in the neonatal intensive care unit.Assessment: Images were retrospectively respiratory-gated using the motion-modulated time-course of the k-space center. Tracheal surfaces were generated from segmentations of end-expiration/inspiration images and analyzed geometrically along the tracheal length to calculate percent-change in luminal cross-sectional area (A % ) and ratio of minor-to-major diameters at end-expiration (r D,exp ). Geometric results were compared to clinically available bronchoscopic findings (n = 14).Statistical Tests: Two-sample t-test.Results: Maximum A % significantly identified subjects with/without a bronchoscopic TM diagnosis (with: 46.9 ± 10.0%; without: 27.0 ± 5.8%; P < 0.001), as did minimum r D,exp (with: 0.346 ± 0.146; without: 0.671 ± 0.218; P = 0.008). Subjects with severe BPD exhibited a far larger range of minimum r D,exp than subjects with mild/moderate BPD or controls (0.631 ± 0.222, 0.782 ± 0.075, and 0.776 ± 0.030, respectively), while minimum r D,exp was reduced in CDH subjects (0.331 ± 0.171) compared with controls (P < 0.001).Data Conclusion: Respiratory-gated UTE MRI can quantitatively and safely evaluate neonatal dynamic tracheal collapse, as validated with the clinical standard of bronchoscopy, without requiring invasive procedures, anesthesia, or ionizing radiation.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:659-667. [ABSTRACT FROM AUTHOR]

Purpose: A novel technique is presented for retrospective estimation and removal of gas‐phase hyperpolarized Xenon‐129 (HP 129Xe) from images of HP 129Xe dissolved in the barrier (comprised of parenchymal lung tissue and blood plasma) and red blood cell (RBC) phases. The primary aim is mitigating RF pulse performance limitations on measures of gas exchange (e.g., barrier–gas and RBC–gas ratios). Correction for gas contamination would simplify technical dissemination of HP 129Xe applications across sites with varying hardware performance, scanner vendors, and models. Methods: Digital lung phantom and human subject experiments (N = 8 healthy; N = 1 with idiopathic pulmonary fibrosis) were acquired with 3D radial trajectory and 1‐point Dixon spectroscopic imaging to assess the correction method for mitigating barrier and RBC imaging artifacts. Dependence of performance on TE, image SNR, and gas contamination level were characterized. Inter‐ and intra‐subject variation in the dissolved‐phase ratios were quantified and compared to human subject experiments before and after correction. Results: Gas contamination resulted in image artifacts similar to those in disease that were mitigated after correction in both simulated and human subject data; for simulation experiments performance varied with TE, but was independent of image SNR and the amount of gas contamination. Artifacts and variation of barrier and RBC components were reduced after correction in both simulation and healthy human lungs (barrier, P = 0.01; RBC, P = 0.045). Conclusion: The proposed technique significantly reduced regional variations in barrier and RBC ratios, separated using a 1‐point Dixon approach, with improved accuracy of dissolved‐phase HP 129Xe images confirmed in simulation experiments. [ABSTRACT FROM AUTHOR]

Background: A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research.Purpose: To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage.Study Type: Volunteer and patient repeatability.Population: Eighteen human subjects (five asthma, six CF, and seven normal subjects).Field Strength/sequence: Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T.Assessment: Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map.Statistical Tests: The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC).Results: Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons).Data Conclusion: 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test-retest repeatability.Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1287-1297. [ABSTRACT FROM AUTHOR]

The purpose of this work was to quantify the redistribution of ventilation-weighted signal in the lungs of asthmatic subjects during a breath-hold using high temporal-spatial resolution hyperpolarized (HP) He-3 MRI. HP He-3 MRI was used to obtain time-resolved, volumetric images of lung ventilation during breath-hold in 39 human subjects classified as either healthy/nondiseased (n = 14), mild-to-moderate asthmatic (n = 17), or severely asthmatic (n = 8). Signals were normalized to a standard lung volume, so that voxels within the lung from all 39 subjects could be analyzed as a group to increase statistical power and enable semiautomated classification of voxels into 1 of 5 ventilation level categories (ranging from defect to hyperintense). End-inspiratory ventilation distribution and temporal rates of mean signal change for each of the five ventilation categories were compared using ANOVA. Time rates of signal change were hypothesized to represent underlying gas redistribution processes, potentially influenced by disease. We found that mild-to-moderate asthmatic subjects showed the greatest rate of signal change, even though those with severe asthma had the greatest end-inspiration ventilation heterogeneity. The observed results support the existence of local differences in airway resistances associated with the different obstructive patterns in the lungs for severe vs. mild-to-moderate asthmatic subjects. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) time series analysis is typically performed using only the magnitude portion of the data. The phase information remains unused largely due to its sensitivity to temporal variations in the magnetic field unrelated to the functional response of interest. These phase changes are commonly the result of physiologic processes such as breathing or motion either inside or outside the imaging field of view. As a result, although the functional phase response carries pertinent physiological information concerning the vasculature, one aspect of which is the location of large draining veins, the full hemodynamic phase response is understudied and is poorly understood, especially in comparison with the magnitude response. It is likely that the magnitude and phase contain disjoint information, which could be used in tandem to better characterize functional hemodynamics. In this work, simulated and human fMRI experimental data are used to demonstrate how statistical analysis of complex-valued fMRI time series can be problematic, and how robust analysis using these powerful and flexible complex-valued statistics is possible through postprocessing with correction for dynamic magnetic field fluctuations in conjunction with estimated motion parameters. These techniques require no special pulse sequence modifications and can be applied to any complex-valued echo planar imaging data set. This analysis shows that the phase component appears to contain information complementary to that in the magnitude and that processing and analysis techniques are available to investigate it in a robust and flexible manner. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background . Thoracoabdominal MRI is limited by respiratory motion, especially in populations who cannot perform breath-holds. One approach for reducing motion blurring in radially-acquired MRI is respiratory gating. Straightforward 'hard-gating' uses only data from a specified respiratory window and suffers from reduced SNR. Proposed 'soft-gating' reconstructions may improve scan efficiency but reduce motion correction by incorporating data with nonzero weight acquired outside the specified window. However, previous studies report conflicting benefits, and importantly the choice of soft-gated weighting algorithm and effect on image quality has not previously been explored. The purpose of this study is to map how variable soft-gated weighting functions and parameters affect signal and motion blurring in respiratory-gated reconstructions of radial lung MRI, using neonates as a model population. Methods . Ten neonatal inpatients with respiratory abnormalities were imaged using a 1.5 T neonatal-sized scanner and 3D radial ultrashort echo-time (UTE) sequence. Images were reconstructed using ungated, hard-gated, and several soft-gating weighting algorithms (exponential, sigmoid, inverse, and linear weighting decay outside the period of interest), with %N proj representing the relative amount of data included. The apparent SNR (aSNR) and motion blurring (measured by the maximum derivative of image intensity at the diaphragm, MDD) were compared between reconstructions. Results . Soft-gating functions produced higher aSNR and lower MDD than hard-gated images using equivalent %N proj , as expected. aSNR was not identical between different gating schemes for given %N proj . While aSNR was approximately linear with %N proj for each algorithm, MDD performance diverged between functions as %N proj decreased. Algorithm performance was relatively consistent between subjects, except in images with high noise. Conclusion . The algorithm selection for soft-gating has a notable effect on image quality of respiratory-gated MRI; the timing of included data across the respiratory phase, and not simply the amount of data, plays an important role in aSNR. The specific soft-gating function and parameters should be considered for a given imaging application's requirements of signal and sharpness., (© 2024 IOP Publishing Ltd.)

A measure of regional gas exchange on HP 129 Xe MRI was able to detect apparent improvements in IPF patients treated with antifibrotic medication after 1 year, while no such improvements were found in patients treated with conventional therapies https://bit.ly/3ZXipzD., Competing Interests: Conflict of interest: A.D. Hahn reports support for the present manuscript from the NIH/NHLBI, American Lung Association and GE Healthcare; and grants or contracts and consulting fees from Polarean PLC outside the submitted work. Conflict of interest: K.J. Carey reports grants or contracts and consulting fees from Imbio Inc., and stock options in Imbio Inc.; and is an employee of Imbio Inc. (all disclosures made outside the submitted work). Conflict of interest: G.P. Barton reports support for the present manuscript from NIAID T32AI007635. Conflict of interest: L.A. Torres reports support for the present manuscript from Flywheel. Conflict of interest: J. Kammerman reports grants or contracts from Polarean PLC outside the submitted work; and patents planned, issued or pending with the Wisconsin Alumni Research Foundation (coinventor on patent related to xenon MRI held by WARF). Conflict of interest: M.L. Schiebler reports support for the present manuscript from the NIH/HLBI; and grants or contracts from the DHHS, PHS, NIH and NIH/NHLBI, outside the submitted work; is the deputy editor of Radiology; and is a shareholder in X-Vax, Inc., Elucent Medical, Inc. and Elucida Oncology, Inc. Conflict of interest: S.B. Fain reports support for the present manuscript from the NIH/NHLBI, American Lung Association and GE Healthcare; grants or contracts from Polarean PLC outside the submitted work; consulting fees from Sanofi/Regeneron and Polarean PLC, outside the submitted work; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi/Regeneron and Polarean PLC. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 ( 129 Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression. Materials and Methods In a prospective study, healthy volunteers and participants with IPF were consecutively recruited between December 2015 and August 2019 and underwent baseline HP 129 Xe MRI and chest CT. Participants with IPF were followed up with forced vital capacity percent predicted (FVC%p), diffusing capacity of the lungs for carbon monoxide percent predicted (DLco%p), and clinical outcome at 1 year. IPF progression was defined as reduction in FVC%p by at least 10%, reduction in DLco%p by at least 15%, or admission to hospice care. CT and MRI were spatially coregistered and a measure of pulmonary gas transfer (red blood cell [RBC]-to-barrier ratio) and high-ventilation percentage of lung volume were compared across groups and across fibrotic versus normal-appearing regions at CT by using Wilcoxon signed rank tests. Results Sixteen healthy volunteers (mean age, 57 years ± 14 [SD]; 10 women) and 22 participants with IPF (mean age, 71 years ± 9; 15 men) were evaluated, as follows: nine IPF progressors (mean age, 72 years ± 7; five women) and 13 nonprogressors (mean age, 70 years ± 10; 11 men). Reduction of high-ventilation percent (13% ± 6.1 vs 8.2% ± 5.9; P = .03) and RBC-to-barrier ratio (0.26 ± 0.06 vs 0.20 ± 0.06; P = .03) at baseline were associated with progression of IPF. Participants with progressive disease had reduced RBC-to-barrier ratio in structurally normal-appearing lung at CT (0.21 ± 0.07 vs 0.28 ± 0.05; P = .01) but not in fibrotic regions of the lung (0.15 ± 0.09 vs 0.14 ± 0.04; P = .62) relative to the nonprogressive group. Conclusion In this preliminary study, functional measures of gas transfer and ventilation measured with xenon 129 MRI and the extent of fibrotic structure at CT were associated with idiopathic pulmonary fibrosis disease progression. Differences in gas transfer were found in regions of nonfibrotic lung. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gleeson and Fraser in this issue.

Infants admitted to the neonatal intensive care unit (NICU) often suffer from multifaceted pulmonary morbidities that are not well understood. Ultrashort echo time (UTE) magnetic resonance imaging (MRI) is a promising technique for pulmonary imaging in this population without requiring exposure to ionizing radiation. The aims of this study were to investigate the effect of neonatal pulmonary disease on R 2 * and tissue density and to utilize numerical simulations to evaluate the effect of different alveolar structures on predicted R 2 *.This was a prospective study, in which 17 neonatal human subjects (five control, seven with bronchopulmonary dysplasia [BPD], five with congenital diaphragmatic hernia [CDH]) were enrolled. Twelve subjects were male and five were female, with postmenstrual age (PMA) at MRI of 39.7 ± 4.7 weeks. A 1.5T/multiecho three-dimensional UTE MRI was used. Pulmonary R 2 * and tissue density were compared across disease groups over the whole lung and regionally. A spherical shell alveolar model was used to predict the expected R 2 * over a range of tissue densities and tissue susceptibilities. Tests for significantly different mean R 2 * and tissue densities across disease groups were evaluated using analysis of variance, with subsequent pairwise group comparisons performed using t tests. Lung tissue density was lower in the ipsilateral lung in CDH compared to both controls and BPD patients (both p < 0.05), while only the contralateral lung in CDH (CDHc) had higher whole-lung R 2 * than both controls and BPD (both p < 0.05). R 2 * differences were significant between controls and CDHc within all tissue density ranges (all p < 0.05) with the exception of the 80%-90% range (p = 0.17). Simulations predicted an inverse relationship between alveolar tissue density and R 2 * that matches empirical human data. Alveolar wall thickness had no effect on R 2 * independent of density (p = 1). The inverse relationship between R 2 * and tissue density is influenced by the presence of disease globally and regionally in neonates with BPD and CDH in the NICU. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: Novel demonstration of R 2 ∗ and tissue density estimation in infant lungs using 3D ultrashort echo time MRI. Differences between adult and neonates with no clinical indication of lung pathology is explored, as well as relationships between parameter estimates and gravitationally dependent position and lung inflation state. This provides a tool for probing physiologic processes that may be relevant to pulmonary disease and progression in newborns., Methods: R 2 ∗ and tissue density were estimated in a phantom consisting of standards allowing for ground truth comparisons and in human subjects (N = 5 infants, N = 4 adults, no clinical indication of lung dysfunction) using a 3D radial multiecho ultrashort echo time MRI sequence. Whole lung averages were compared between infants and adults. Dependence of the metrics on anterior-posterior position as well as between end-tidal inspiration and expiration were explored, in addition to the general relationship between R 2 ∗ and tissue density., Results: Estimates in the phantom did not differ significantly from ground truth. Neonates had significantly lower mean R 2 ∗ (P = .006) and higher mean tissue density (P = 1.5e-5) than adults. Tissue density and R 2 ∗ were both significantly dependent on anterior-posterior position and lung inflation state (P < .005). An overall inverse relationship was found between R 2 ∗ and tissue density, which was similar in both neonates and adults., Conclusion: Estimation of tissue density and R 2 ∗ in free breathing, nonsedated, neonatal patients is feasible using multiecho ultrashort echo time MRI. R 2 ∗ was no different between infants and adults when matched for tissue density, although density of lung parenchyma was, on average, lower in adults than neonates., (© 2019 International Society for Magnetic Resonance in Medicine.)