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This study introduces a novel technique of generating high-resolution 3D ventilation maps from hyperpolarized helium-3 MRI. It is the first study to demonstrate that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.

Background Hyperpolarized gas with helium (HHe-3) MR (magnetic resonance) is a noninvasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes. Purpose To determine if VH indicators quantified by HHe-3 MR imaging (MRI) predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze or asthma. Methods Sixty children with poorly-controlled wheeze or asthma underwent HHe-3 MRI, including 22 with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined four ventilation compartments. The non-ventilated and hypoventilated compartments divided by the total lung volume defined a VH index (VHI %). Results Children with VHI % in the upper quartile had significantly greater airflow limitation, bronchodilator responsiveness, blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic or neutrophilic granulocyte patterns compared to children with VHI % in the lower quartile. Lavage return from hypoventilated bronchial segments had greater eosinophil % than from ventilated segments. Conclusion In children with asthma, greater VHI % as measured by HHe-3 MRI identifies a severe phenotype with higher type 2 inflammatory markers, and maps to regions of lung eosinophilia. Listed on ClinicalTrials. gov (NCT02577497).

BACKGROUND: Hyperpolarized helium 3 magnetic resonance imaging ((3)He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children. OBJECTIVE: To evaluate the safety of (3)He MRI in children and adolescents with asthma. MATERIALS AND METHODS: This was a retrospective observational study. (3)He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8–18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 (3)He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO(2)) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8–12 years, 13–15 years, 16–18 years) using linear mixed-effects models. RESULTS: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO(2) after (3)He MRI. The youngest age group (8–12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after (3)H inhalation, and an increased SpO(2) post MRI. CONCLUSION: The use of (3)He MRI is safe in children and adolescents with asthma.

Hyperpolarized helium 3 diffusion-weighted MRI metrics were elevated in lungs with idiopathic pulmonary fibrosis, and diffusion model estimates of airway mean diffusive length scale demonstrated se...

Background Hyperpolarized noble gas MRI helps measure lung ventilation, but clinical translation remains limited. Free-breathing proton MRI may help quantify lung function using existing MRI systems without contrast material and may assist in providing information about ventilation not visible to the eye or easily extracted with segmentation methods. Purpose To explore the use of deep convolutional neural networks (DCNNs) to generate synthetic MRI ventilation scans from free-breathing MRI (deep learning [DL] ventilation MRI)-derived specific ventilation maps as a surrogate of noble gas MRI and to validate this approach across a wide range of lung diseases. Materials and Methods In this secondary analysis of prospective trials, 114 paired noble gas MRI and two-dimensional free-breathing MRI scans were obtained in healthy volunteers with no history of chronic or acute respiratory disease and in study participants with a range of different obstructive lung diseases, including asthma, bronchiectasis, chronic obstructive pulmonary disease, and non-small-cell lung cancer between September 2013 and April 2018 (ClinicalTrials.gov identifiers: NCT03169673, NCT02351141, NCT02263794, NCT02282202, NCT02279329, and NCT02002052). A U-Net-based DCNN model was trained to map free-breathing proton MRI to hyperpolarized helium 3 (3He) MRI ventilation and validated using a sixfold validation. During training, the DCNN ventilation maps were compared with noble gas MRI scans using the Pearson correlation coefficient (r) and mean absolute error. DCNN ventilation images were segmented for ventilation and ventilation defects and were compared with noble gas MRI scans using the Dice similarity coefficient (DSC). Relationships were evaluated with the Spearman correlation coefficient (rS). Results One hundred fourteen study participants (mean age, 56 years ± 15 [standard deviation]; 66 women) were evaluated. As compared with 3He MRI, DCNN model ventilation maps had a mean r value of 0.87 ± 0.08. The mean DSC for DL ventilation MRI and 3He MRI ventilation was 0.91 ± 0.07. The ventilation defect percentage for DL ventilation MRI was highly correlated with 3He MRI ventilation defect percentage (rS = 0.83, P < .001, mean bias = -2.0% ± 5). Both DL ventilation MRI (rS = -0.51, P < .001) and 3He MRI (rS = -0.61, P < .001) ventilation defect percentage were correlated with the forced expiratory volume in 1 second. The DCNN model required approximately 2 hours for training and approximately 1 second to generate a ventilation map. Conclusion In participants with diverse pulmonary pathologic findings, deep convolutional neural networks generated ventilation maps from free-breathing proton MRI trained with a hyperpolarized noble-gas MRI ventilation map data set. The maps showed correlation with noble gas MRI ventilation and pulmonary function measurements. © RSNA, 2020 See also the editorial by Vogel-Claussen in this issue.

BACKGROUND: Apparent diffusion coefficient (ADC) maps of inhaled hyperpolarized gases have shown promise in the characterization of emphysema in patients with chronic obstructive pulmonary disease (COPD), yet an easily interpreted quantitative metric beyond mean and standard deviation has not been established. PURPOSE: To introduce a quantitative framework with which to characterize emphysema burden based on hyperpolarized helium 3 ((3)He) and xenon 129 ((129)Xe) ADC maps and compare its diagnostic performance with CT-based emphysema metrics and pulmonary function tests (PFTs). MATERIALS AND METHODS: Twenty-seven patients with mild, moderate, or severe COPD and 13 age-matched healthy control subjects participated in this retrospective study. Participants underwent CT and multiple b value diffusion-weighted (3)He and (129)Xe MRI examinations and standard PFTs between August 2014 and November 2017. ADC-based emphysema index was computed separately for each gas and b value as the fraction of lung voxels with ADC values greater than in the healthy group 99th percentile. The resulting values were compared with quantitative CT results (relative lung area 0.99) and strongly correlated with quantitative CT (r = 0.86, P < .001 for (3)He; r = 0.85, P < .001 for (129)Xe) with high AUC (≥0.93; 95% confidence interval [CI]: 0.85, 1.00). ADC emphysema indices were also correlated with percentage of predicted diffusing capacity of lung for carbon monoxide (r = −0.81, P < .001 for (3)He; r = −0.80, P < .001 for (129)Xe) and percentage of predicted residual lung volume divided by total lung capacity (r = 0.65, P < .001 for (3)He; r = 0.61, P < .001 for (129)Xe). CONCLUSION: Emphysema index based on hyperpolarized helium 3 or xenon 129 diffusion MRI provides a repeatable measure of emphysema burden, independent of gas or b value, with similar diagnostic performance as quantitative CT or pulmonary function metrics. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schiebler and Fain in this issue.

Purpose To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 (3He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF). Materials and Methods In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10-55 years (14 male; age range, 13-55 years; 11 female; age range, 10-37 years) successfully underwent pulmonary function tests, hyperpolarized 3He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1-2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized 3He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability. Results In all 24 participants, the global VDP measurements from either OE MRI (ρ = -0.66, P < .001) or hyperpolarized 3He MRI (ρ = -0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized 3He MRI. Both OE MRI-based VDP and hyperpolarized 3He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001). Conclusion In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized 3He MRI for quantitative measures of ventilation defects and their repeatability. © RSNA, 2018 Online supplemental material is available for this article.

Purpose To develop and apply an image acquisition and analysis strategy for spatial comparison of CT-ventilation images with hyperpolarized gas MRI. Methods 11 lung cancer patients underwent 129Xe and 3He ventilation MRI and co-registered 1H anatomical MRI. Expiratory and inspiratory breath-hold CTs were used for deformable image registration and calculation of three CT-ventilation metrics: Hounsfield unit (CTHU), Jacobian (CTJac) and specific gas volume change (CTSGV). Inspiration CT and hyperpolarized gas ventilation MRI were registered via same-breath anatomical 1H-MRI. Voxel-wise Spearman correlation coefficients were calculated between each CT-ventilation image and its corresponding 3He/129Xe-MRI, and for the mean values in regions of interest (ROIs) ranging from fine to coarse in-plane dimensions of 5x5, 10x10, 15x15 and 20x20, located within the lungs as defined by the same-breath 1H-MRI lung mask. Correlation of 3He and 129Xe-MRI was also assessed. Results Spatial correlation of CT-ventilation against 3He/129Xe-MRI increased with ROI size. For example, for CTHU, mean±SD Spearman coefficients were 0.37±0.19/0.33±0.17 at the voxel-level and 0.52±0.20/0.51±0.18 for 20x20 ROIs, respectively. Correlations were stronger for CTHU than for CTJac or CTSGV. Correlation of 3He with 129Xe-MRI was consistently higher than either gas against CT-ventilation maps over all ROIs (p

Rationale and Objectives To determine lobar ventilation patterns in asthmatic lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI). Materials and Methods Eighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20 severe asthma) underwent HP 3He MRI, computed tomography (CT), and pulmonary function testing. After registering proton to 3He images, we segmented the lungs from proton MRI and further segmented the five lung lobes (right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and left lower lobe [LLL]) by referring to the lobar segmentation from CT. We classified the gas volume into four signal intensity levels as follows: ventilation defect percent (VDP), low ventilation percent, medium ventilation percent, and high ventilation percent. The local signal intensity variations in the ventilated volume were estimated using heterogeneity score (Hs). We compared each ventilation level and Hs measured in the whole lung and lobar regions across the three subject groups. Results In mild-to-moderate asthma, the RML and RUL showed significantly greater VDP than the two lower lobes (RLL and LLL) (P ≤ .047). In severe asthma, the pattern was more variable with the VDP in the RUL significantly greater than in the RLL (P = .026). In both asthma groups, the lower lobes (RLL and LLL) showed significantly higher high ventilation percent and Hs compared to the three upper lobes (all P ≤ .015). Conclusions In asthma, the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL were more highly ventilated with greater local heterogeneity. These findings may facilitate guided bronchoscopic sampling and localized airway treatment in future studies.

Purpose To assess the magnitude of regional response to respiratory therapeutic agents in the lungs by using treatment response mapping (TRM) with hyperpolarized gas magnetic resonance (MR) imaging. TRM was used to quantify regional physiologic response in adults with asthma who underwent a bronchodilator challenge. Materials and Methods This study was approved by the national research ethics committee and was performed with informed consent. Imaging was performed in 20 adult patients with asthma by using hyperpolarized helium 3 (3He) ventilation MR imaging. Two sets of baseline images were acquired before inhalation of a bronchodilating agent (salbutamol 400 μg), and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), was calculated as the difference in regional gas distribution (R[r] = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global treatment response map (ΔRnet) was then used as a global lung index for comparison with metrics of bronchodilator response measured by using spirometry and the global imaging metric percentage ventilated volume (%VV). Results ΔRnet showed significant correlation (P < .01) with changes in forced expiratory volume in 1 second (r = 0.70), forced vital capacity (r = 0.84), and %VV (r = 0.56). A significant (P < .01) positive treatment effect was detected with all metrics; however, ΔRnet showed a lower intersubject coefficient of variation (64%) than all of the other tests (coefficient of variation, ≥99%). Conclusion TRM provides regional quantitative information on changes in inhaled gas ventilation in response to therapy. This method could be used as a sensitive regional outcome metric for novel respiratory interventions. © RSNA, 2017 Online supplemental material is available for this article.

Purpose To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. Materials and methods HHe ventilation MRI was performed on seven children ≤ 4 years old. Contiguous 2D–spiral helium-3 images were acquired sequentially with a scan time of ≤ 0.2 s/slice. Results Motion-artifact–free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained. Gas was homogeneously distributed in healthy individuals; focal ventilation defects were found in patients with respiratory diseases. Conclusion HHe ventilation MRI can aid assessment of pediatric lung disease even at a young age.

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre- and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV1 at follow-up, and differences between reversible and not-reversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV1 reversibility at follow-up. Results: Eleven participants with asthma (mean age, 42 years ± 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months ± 7. Medications, exacerbations, FEV1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV1 by 20% (PC20) was greater in FEV1-irreversible participants at follow-up (P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up (R 2 = 0.80; P < .01), but PC20, age, and FEV1 did not (R 2 = 0.63; P = .15). Conclusion: MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months ± 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations.

Background This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3 He-magnetic resonance imaging (MRI)–defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D - CFTR mutation. Methods Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). Results Mean change in TVD ranged from −8.2% (p=0.0547) to −12.8% (p=0.0078) in Part A (n=8) and −6.3% (p=0.1953) to −9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. Conclusions TVD responded to ivacaftor therapy. 3 He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537

Purpose To evaluate T2, T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 (3He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. Methods Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3He dose. Results As expected, T2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. Conclusions Hyperpolarized 3He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Rationale and Objectives This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K -means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB). Materials and Methods Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K -means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement. Results The adaptive K -means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K -means ( ρ = −0.64, P 0.0001) and by the manual method ( ρ = −0.63, P 0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort. Conclusions Compared to the manual method, the adaptive K -means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases.

To determine whether hyperpolarized helium 3 magnetic resonance (MR) imaging to measure alveolar partial pressure of oxygen (Pao2) shows sufficient test-retest repeatability and between-cohort differences to be used as a reliable technique for detection of alterations in gas exchange in asymptomatic smokers.The protocol was approved by the local institutional review board and was HIPAA compliant. Informed consent was obtained from all subjects. Two sets of MR images were obtained 10 minutes apart in 25 subjects: 10 nonsmokers (five men, five women; mean ± standard deviation age, 50 years ± 6) and 15 smokers (seven women, eight men; mean age, 50 years ± 8). A mixed-effects model was developed to identify the regional repeatability of Pao2 measurements as an intraclass correlation coefficient. Ten smokers were matched with the 10 nonsmokers on the basis of signal-to-noise ratio (SNR). Three separate models were generated: one for nonsmokers, one for the SNR-matched smokers, and one for the five remaining smokers, who were imaged with a significantly higher SNR.Short-term back-to-back regional reproducibility was assessed by using intraclass correlation coefficients, which were 0.67 and 0.65 for SNR case-matched nonsmokers and smokers, respectively. Repeatability was a strong function of SNR; a 50% increase in SNR in the remaining smokers improved the intraclass correlation coefficient to 0.82. Although repeatability was not significantly different between the SNR-matched cohorts (P = .44), the smoker group showed higher spatial and temporal variability in Pao2.The short-term test-retest repeatability of hyperpolarized gas MR imaging of regional Pao2 was good. Asymptomatic smokers exhibited greater spatial and temporal variability in Pao2 than did the nonsmokers, which suggests that this parameter allows detection of small functional alterations associated with smoking.

Purpose To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 (3He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths. Materials and Methods Hyperpolarized 3He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions. Results ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm2/s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm2/s, respectively; P < 0.05). Conclusion These findings indicate that diffusion-weighted hyperpolarized 3He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces. J. Magn. Reson. Imaging 2015.

Purpose: To measure regional specific ventilation with free-breathing hydrogen 1 (1H) magnetic resonance (MR) imaging without exogenous contrast material and to investigate correlations with hyperpolarized helium 3 (3He) MR imaging and pulmonary function test measurements in healthy volunteers and patients with asthma. Materials and Methods: Subjects underwent free-breathing 1H and static breath-hold hyperpolarized 3He MR imaging as well as spirometry and plethysmography; participants were consecutively recruited between January and June 2017. Free-breathing 1H MR imaging was performed with an optimized balanced steady-state free-precession sequence; images were retrospectively grouped into tidal inspiration or tidal expiration volumes with exponentially weighted phase interpolation. MR imaging volumes were coregistered by using optical flow deformable registration to generate 1H MR imaging-derived specific ventilation maps. Hyperpolarized 3He MR imaging- and 1H MR imaging-derived specific ventilation maps were coregistered to quantify regional specific ventilation within hyperpolarized 3He MR imaging ventilation masks. Differences between groups were determined with the Mann-Whitney test and relationships were determined with Spearman (ρ) correlation coefficients. Statistical analyses were performed with software. Results: Thirty subjects (median age: 50 years; interquartile range [IQR]: 30 years), including 23 with asthma and seven healthy volunteers, were evaluated. Both 1H MR imaging-derived specific ventilation and hyperpolarized 3He MR imaging-derived ventilation percentage were significantly greater in healthy volunteers than in patients with asthma (specific ventilation: 0.14 [IQR: 0.05] vs 0.08 [IQR: 0.06], respectively, P < .0001; ventilation percentage: 99% [IQR: 1%] vs 94% [IQR: 5%], P < .0001). For all subjects, 1H MR imaging-derived specific ventilation correlated with plethysmography-derived specific ventilation (ρ = 0.54, P = .002) and hyperpolarized 3He MR imaging-derived ventilation percentage (ρ = 0.67, P < .0001) as well as with forced expiratory volume in 1 second (FEV1) (ρ = 0.65, P = .0001), ratio of FEV1 to forced vital capacity (ρ = 0.75, P < .0001), ratio of residual volume to total lung capacity (ρ = -0.68, P < .0001), and airway resistance (ρ = -0.51, P = .004). 1H MR imaging-derived specific ventilation was significantly greater in the gravitational-dependent versus nondependent lung in healthy subjects (P = .02) but not in patients with asthma (P = .1). In patients with asthma, coregistered 1H MR imaging specific ventilation and hyperpolarized 3He MR imaging maps showed that specific ventilation was diminished in corresponding 3He MR imaging ventilation defects (0.05 ± 0.04) compared with well-ventilated regions (0.09 ± 0.05) (P < .0001). Conclusion: 1H MR imaging-derived specific ventilation correlated with plethysmography-derived specific ventilation and ventilation defects seen by using hyperpolarized 3He MR imaging. © RSNA, 2018 Online supplemental material is available for this article.

Purpose: In MR-velocity phase-contrast measurements, increasing the encoding bipolar gradient, i.e., decreasing the field of speed, usually improves measurement precision. However, in gases, fast diffusion during the bipolar gradient pulses may dramatically decrease the signal-to-noise ratio, thus degrading measurement precision. These two effects are contradictory. This work aims at determining the optimal sequence parameters to improve the velocity measurement precision. Theory and Methods: This work presents the theoretical optimization of bipolar gradient parameters (duration and amplitude) to improve velocity measurement precision. An analytical approximation is given as well as a numerical optimization. It is shown that the solution depends on the diffusion coefficient and T 2 ∗. Experimental validation using hyperpolarized 3He diluted in various buffer gases (4He, N 2 , and SF 6 ) is presented at 1.5 Tesla (T) in a straight pipe. Results: Excellent agreement was found with the theoretical results for prediction of optimal field of speed and good agreement was found for the precision in measured velocity, but for SF6 buffered gas. Conclusion: The theoretical predictions were validated, providing a way to optimize velocity mapping in gases.

Rationale and Objectives In this review, we summarize our experience evaluating pulmonary function in 330 different subjects using hyperpolarized noble gas magnetic resonance imaging (MRI) after enrollment and screening of >1100 subjects with and without respiratory disease during the period February 1, 2006, through November 1, 2012. Materials and Methods We discuss the feasibility of hyperpolarized gas MRI research in a small nonhospital research unit and provide an overview of our experience since we initiated patient-based studies. We also discuss the importance of infrastructure support, collaboration, research trainees, and a large and willing patient population that helped to advance the research and technological deliverables. A summary of patient safety and tolerability, key feasibility, and research milestones is provided, as well as a roadmap for future studies. Results Hyperpolarized 3He and 129Xe gas MRI is feasible at smaller centers without significant human resources for large and small longitudinal studies by virtue of its excellent patient safety and tolerability, the speed with which images can be acquired and quantitatively analyzed and the high spatial-temporal dynamics of the method that allows for acute and chronic therapy studies. Conclusions The hyperpolarized noble gas MRI community's highly collaborative efforts and motivation to further the development and application of this tool has resulted in a moment-of-opportunity to translate the method clinically to provide an improved understanding of pulmonary disease. There are, as well, new and unprecedented opportunities for the evaluation of disease progression and to help develop the new treatments and interventions critically required for chronic pulmonary disease.

Purpose To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. Materials and Methods Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. Results One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a “control” or a “smoker,” based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as “smokers” indicating an elevation of the ADC AUC. Conclusion Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage. J. Magn. Reson. Imaging 2014;39:77–84. © 2013 Wiley Periodicals, Inc.

Purpose To investigate the utility of hyperpolarized He-3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects were recruited with Exercise Induced Bronchoconstriction (EIB), a condition described by airway constriction following exercise leading to reduced Forced Expiratory Volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He-3 MRI.

The aim of the study was to determine whether hyperpolarized He diffusion-weighted magnetic resonance imaging detects abnormalities in the lungs in children with bronchopulmonary dysplasia (BPD) as compared with age-matched normal children.All experiments were compliant with Health Insurance Portability and Accountability Act (HIPAA) and performed with Food and Drug Administration approval under an IND application. The protocol was approved by our Institutional Review Board, and written informed consent was obtained. Hyperpolarized He diffusion-weighted magnetic resonance imaging was performed in 16 subjects with a history of preterm birth complicated by BPD (age range, 6.8 to 13.5 y; mean, 9.0 y) and in 29 healthy term-birth subjects (age range, 4.5-14.7 y; mean, 9.2 y) using a gradient-echo sequence with bipolar diffusion gradients and with measurements at 2 b values (0 and 1.6 s/cm). Age-related comparison of the whole-lung mean apparent diffusion coefficient (ADC), 90th percentile ADC, and percentage of whole-lung volume with ADC0.2 cm/s between the 2 groups was examined using ordinary least-squares multiple regression.The mean ADC was significantly greater in subjects with BPD (0.187 vs. 0.152 cm/s, P0.001). The 90th percentile ADC and mean percentage lung volume with ADC0.2 cm/s were also higher in the BPD group (0.258 vs. 0.215 cm/s, 30.3% vs. 11.9%, P0.001 for both). The body surface area-adjusted ventilated lung volume was similar in the 2 groups (1.93 vs. 1.91 L, P=0.90).Children with BPD had higher ADCs and the same lung volumes when compared with age-matched healthy subjects, suggesting that children with BPD have enlarged alveoli that are reduced in number.

The objective of this study was to evaluate the regional effects of bronchodilator administration in chronic obstructive pulmonary disease (COPD) using hyperpolarized helium-3 (3He) MRI apparent diffusion coefficient (ADC). Ten COPD ex-smokers provided written, informed consent and underwent diffusion-weighted, hyperpolarized 3He MRI, spirometry, and plethysmography before and 25 ± 2 min after bronchodilator administration. Pre- and postsalbutamol whole-lung (WL) ADC maps were generated and registered together to identify the lung regions containing the 3He signal at both time points, and mean ADC within those regions of interest (ROI) was determined for a measurement of previously ventilated ROI ADC (ADCP). Lung ROI with 3He signal at both time points was used as a binary mask on postsalbutamol WL ADC maps to obtain an ADC measurement for newly ventilated ROI (ADCN). Postsalbutamol, no significant differences were detected in WL ADC ( P = 0.516). There were no significant differences between ADCN and ADCP postsalbutamol ( P = 1.00), suggesting that the ADCN lung regions were not more emphysematous than the lung ROI participating in ventilation before bronchodilator administration. Postsalbutamol, a statistically significant decrease in ADCP ( P = 0.01) was detected, and there were significant differences between ADCP in the most anterior and most posterior image slices ( P = 0.02), suggesting a reduction in regional gas trapping following bronchodilator administration. Regional evaluation of tissue microstructure using hyperpolarized 3He MRI ADC provides insights into lung alterations that accompany improvements in regional 3He gas distribution after bronchodilator administration.

Rationale and Objectives The aim of this study was to determine the efficacy of hyperpolarized 3He (HHe) ventilation and apparent diffusion coefficient (ADC) HHe magnetic resonance imaging (MRI) in detecting changes in lung function and microstructure in emphysematous lung after bronchial valve (BV) placement. Materials and Methods One patient diagnosed with emphysema had nine BVs placed in upper lobe bronchi. Imaging was performed before and 6 months after BV placement. Coronal HHe ventilation MRI was used to assess volume changes in the ventilated portions of the lung. Coronal ADC HHe MRI, acquired with b value pairs of 0 and 1.6 s/cm2 during a second 10-second breath-hold, was used to compute ADC values. Results HHe ventilation MRI revealed decreased ventilation in the treated segments of the upper lobes after BV placement. Increased ventilation in the lower lobes and two untreated segments of the left upper lobes were also observed, with an upward shift of the major fissure of the right lung. Whole-lung mean ADC decreased by 6.3% from baseline, from 0.48 ± 0.196 to 0.45 ± 0.176 cm2/s (toward healthier values) following BV placement. Conclusions HHe ventilation MRI detected an increase in whole-lung volume and an interlobar fissure shift indicative of increased ventilation of lower relative to upper lobes. Reduced ADC values suggest increased ventilation to healthy lower lobes at the expense of more diseased, expanded alveolar spaces in the upper lobes distal to BV placement. These results suggest that this ionizing radiation–free method of examining the lungs may offer functional and structural information useful in BV intervention planning.

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects.

RATIONALE AND OBJECTIVES: To better understand imaging measurement precision and reproducibility and to provide guidance for measurements in individual cystic fibrosis (CF) subjects, we evaluated CF adults on two occasions 7 ± 2 days apart using spirometry, plethysmography, and hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twelve CF subjects underwent spirometry, plethysmography, and (3)He MRI twice within 7 ± 2 days, reporting (3)He ventilation defect volume (VDV) and ventilation defect percent (VDP). RESULTS: Based on measurement variability, the smallest detectable difference (SDD) for (3)He VDV and VDP was determined to be 120 mL and 2%, respectively. Although no significant difference in spirometry or plethysmography was detected after 7 days, there was a significant difference in mean (3)He VDV (130 mL ± 250 mL, P < .0001) and VDP (3% ± 4%, P < .0001), although baseline and 7-day measurements were highly correlated (VDV: r = .85, P = .001; VDP: r = .94, P < .0001). We estimated the sample sizes required to detect a 5%/7%/10% change in (3)He VDP as 60/15/5 subjects per group. CONCLUSION: Hyperpolarized (3)He MRI VDP measurement precision resulted in an SDD for individual CF subjects of 2%, indicating that changes greater than this can be attributed to lung functional changes and not measurement error. After 7 days, significant changes in mean (3)He VDV and VDP were detected and these changes were not reflected by changes in pulmonary function measurements. These findings demonstrate the high sensitivity and reproducibility of (3)He MRI functional imaging that permits the use of relatively small samples sizes in CF interventional studies.

Purpose—To propose and test the feasibility of a novel method for quantifying 3-D regional pulmonary kinematics from hyperpolarized helium-3 tagged MRI in human subjects using a tailored image processing pipeline and a recently developed nonrigid registration framework. Materials and Methods—Following image acquisition, inspiratory and expiratory tagged helium-3 MR images were preprocessed using various image filtering techniques to enhance the tag surfaces. Segmentation of the three orthogonal sets of tag planes in each lung produced distinct point-set representations of the tag surfaces. Using these labeled point-sets, deformation fields and corresponding strain maps were obtained via nonrigid point-set registration. Kinematic analysis was performed on three volunteers. Results—Tag lines in inspiratory and expiratory images were co-registered producing a continuous 3-D correspondence mapping. Average displacement and directional strains were calculated in three subjects in the inferior, mid, and superior portions of the right and left lungs. As expected, the predominant direction of displacements with expiration is from inferior to superior. Conclusion—Kinematic quantitation of pulmonary motion using tagged helium-3 MRI is feasible using the applied image preprocessing filtering techniques and nonrigid point-set registration. Potential benefits from regional pulmonary kinematic quantitation include the facilitation of diagnosis and local assessment of disease progression.

A computational framework is described that was developed for quantitative analysis of hyperpolarized helium-3 MR lung ventilation image data. This computational framework was applied to a study consisting of 55 subjects (47 asthmatic and eight normal). Each subject was imaged before and after respiratory challenge and also underwent spirometry. Approximately 1600 image features were calculated from the lungs in each image. Both the image and 27 spirometric features were ranked based on their ability to characterize clinical diagnosis using a mutual information-based feature subset selection algorithm. It was found that the top image features perform much better compared with the current clinical gold-standard spirometric values when considered individually. Interestingly, it was also found that spirometric values are relatively orthogonal to these image feature values in terms of informational content.

Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

Diffusion of hyperpolarized helium-3 in epoxy phantoms was experimentally studied by pulsed-gradient nuclear magnetic resonance (NMR). One phantom with a dichotomic branching structure densely filling a cubic volume was built using the Kitaoka algorithm to model a healthy human acinus. Two other phantoms, one with a different size and the other one with a partial destruction of the branched structure, were built to simulate changes occurring at the early stages of emphysema. Gas pressure and composition (mixture with nitrogen) were varied, thus exploring different diffusion regimes. Preliminary measurements in a cylindrical glass cell allowed us to calibrate the gradient intensity with 1% accuracy. Measurements of NMR signal attenuation due to gas diffusion were compared to a classical Gaussian model and to Monte Carlo simulations. In the slow diffusion regime, the Gaussian model was in reasonable agreement with experiments for low gradient intensity, but there was a significant systematic deviation at larger gradient intensity. An apparent diffusion coefficient Dapp was deduced, and in agreement with previous findings, a linear decrease of Dapp/D0 with D0(1/2) was observed, where D0 is the free diffusion coefficient. In the regime of intermediate diffusion, experimental data could be described by the Gaussian model for very small gradient intensities only. The corresponding Dapp/D0 values seemed to reach a constant value. Monte Carlo simulations were generally in fair agreement with the measurements in both regimes. Our results suggest that, for diffusion times typical of medical magnetic resonance imaging, an increase in alveolar size has more impact on signal attenuation than a partial destruction of the branched structure at equivalent surface-to-volume ratio.

Purpose To assess the feasibility and optimize the accuracy of the multibreath wash-in hyperpolarized helium 3 ((3)He) approach to ventilation measurement by using magnetic resonance (MR) imaging as well as to examine the physiologic differences that this approach reveals among nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Materials and Methods All experiments were approved by the local institutional review board and compliant with HIPAA. Informed consent was obtained from all subjects. To measure fractional ventilation, the authors administered a series of identical normoxic hyperpolarized gas breaths to the subject; after each inspiration, an image was acquired during a short breath hold. Signal intensity buildup was fit to a recursive model that regionally solves for fractional ventilation. This measurement was successfully performed in nine subjects: three healthy nonsmokers (one man, two women; mean age, 45 years ± 4), three asymptomatic smokers (three men; mean age, 51 years ± 5), and three patients with COPD (three men; mean age, 59 years ± 5). Repeated measures analysis of variance was performed, followed by post hoc tests with Bonferroni correction, to assess the differences among the three cohorts. Results Whole-lung fractional ventilation as measured with hyperpolarized (3)He in all subjects (mean, 0.24 ± 0.06) showed a strong correlation with global fractional ventilation as measured with a gas delivery device (R(2) = 0.96, P.001). Significant differences between the means of whole-lung fractional ventilation (F2,10 = 7.144, P = .012) and fractional ventilation heterogeneity (F2,10 = 7.639, P = .010) were detected among cohorts. In patients with COPD, the protocol revealed regions wherein fractional ventilation varied substantially over multiple breaths. Conclusion Multibreath wash-in hyperpolarized (3)He MR imaging of fractional ventilation is feasible in human subjects and demonstrates very good global (whole-lung) precision. Fractional ventilation measurement with this physiologically realistic approach reveals significant differences between patients with COPD and healthy subjects. To minimize error, several sources of potential bias must be corrected when calculating fractional ventilation. (©) RSNA, 2016 Online supplemental material is available for this article.

Purpose: To measure lung motion between end-inhalation and end-exhalation using a hyperpolarized helium-3 (HP 3 He) magnetic resonance (MR) tagging technique. Methods and Materials: Three healthy volunteers underwent MR tagging studies after inhalation of 1 L HP 3 He gas diluted with nitrogen. Multiple-slice two-dimensional and volumetric three-dimensional MR tagged images of the lungs were obtained at end-inhalation and end-exhalation, and displacement vector maps were computed. Results: The grids of tag lines in the HP 3 He MR images were well defined at end-inhalation and remained evident at end-exhalation. Displacement vector maps clearly demonstrated the regional lung motion and deformation that occurred during exhalation. Discontinuity and differences in motion pattern between two adjacent lung lobes were readily resolved. Conclusions: Hyperpolarized helium-3 MR tagging technique can be used for direct in vivo measurement of respiratory lung motion on a regional basis. This technique may lend new insights into the regional pulmonary biomechanics and thus provide valuable information for the deformable registration of lung.

A new technique is demonstrated in six healthy human subjects that combines grid-tagging and hyperpolarized helium-3 MRI to assess regional lung biomechanical function and quantitative ventilation. 2D grid-tagging, achieved by applying sinc-modulated RF-pulse trains along the frequency- and phase-encoding directions, was followed by a multislice fast low-angle shot (FLASH)-based acquisition at inspiration and expiration. The displacement vectors, first and second principal strains, and quantitative ventilation were computed, and mean values were calculated for the upper, middle, and lower lung regions. Displacements in the lower region were significantly greater than those in either the middle or upper region (P < 0.005), while there were no significant differences between the three regions for the two principal strains and quantitative ventilation (P = 0.11–0.92). Variations in principal strains and ventilation were greater between subjects than between lung zones within individual subjects. This technique has the potential to provide insight into regional biomechanical alterations of lung function in a variety of lung diseases. Magn Reson Med 58:373–380, 2007. © 2007 Wiley-Liss, Inc.

Background Accurate characterization of asthma severity is difficult due to the variability of symptoms. Hyperpolarized helium-3 MRI (H3HeMR) is a new technique in which the airspaces are visualized, depicting regions with airflow obstruction as "ventilation defects." The objective of this study was to compare the extent of H3HeMR ventilation defects with measures of asthma severity and spirometry. Methods Patients with a physician diagnosis of asthma and normal control subjects underwent H3HeMR. For each person, the number and size of ventilation defects were scored and the average number of ventilation defects per slice (VDS) was calculated. The correlations of the imaging findings with measures of asthma severity and spirometry were determined. Results There were 58 patients with asthma (mild-intermittent, n=13; mild-persistent, n=13; moderate-persistent, n=20; and severe-persistent, n=12) and 18 control subjects. Mean ± SE VDS for asthmatics was significantly greater than for control subjects (0.99 ± 0.15 vs 0.26 ± 0.22, p=0.004). Among asthmatics, VDS was significantly higher for the group with moderate-persistent and severe-persistent disease than for the group with mild-intermittent and mild-persistent disease (1.37 ± 0.24 vs 0.53 ± 0.12, p Conclusions Regional changes of airflow obstruction in asthmatics depicted by H3HeMR correlate with measures of asthma severity and spirometry.

Rationale and Objectives The purpose of this study is to determine hyperpolarized helium 3 (HHe) magnetic resonance (MR) findings of the lung in patients with cystic fibrosis (CF) compared with healthy subjects and determine whether HHe MR can detect changes after bronchodilator therapy or mechanical airway mucus clearance treatment. Materials and Methods Thirty-one subjects, 16 healthy volunteers and 15 patients with CF, underwent HHe lung ventilation MR imaging and spirometry at baseline. Eight patients with CF then were treated with nebulized albuterol, after which a follow-up HHe MR scan was obtained. Subsequently, recombinant human deoxyribonuclease (DNase) treatment and chest physical therapy were performed in these eight subjects, followed by a third HHe MR scan. For each MR study, the number of ventilation defects was scored by a human reader. Results Patients with CF had significantly more HHe MR ventilation defects per image than healthy subjects (mean, 8.2 defects in patients with CF vs 1.6 defects in healthy subjects; P P = .0002). After treatment with albuterol, there was a small, but statistically significant, decrease in number of ventilation defects (mean, 9.6–8.0 defects; P = .025). After DNase and chest physical therapy, there was a trend toward increasing ventilation defects (mean, 8.3 defects; P = .096), but with a residual net improvement relative to baseline. Conclusion In patients with CF, HHe MR ventilation defects correlate with spirometry, change with treatment, and are elevated in number in patients with CF with normal spirometry results. Thus, HHe MR appears to possess many of the characteristics required of a biomarker for pulmonary CF and may be useful in the evaluation of CF pulmonary disease severity or progression.

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.

Transverse relaxation of hyperpolarized helium-3 magnetization in respiratory airways highly depends on local magnetic field gradients induced by the magnetic susceptibility difference between gas and pulmonary tissue. Fast transverse relaxation is known to be an important feature that yields information about lung microstructure and function, but it is also an essential limitation in designing efficient strategies for lung imaging. Using intravascular injections of a superparamagnetic contrast agent in rats, it was possible to increase the overall susceptibility of the perfused lung tissues and hence to match it with the gas susceptibility. The transverse decay time constant of inhaled hyperpolarized helium-3 was measured in multiple-spin-echo experiments at 1.5 T as a function of the superparamagnetic contrast agent concentration in the animal blood. The time constant was increased by a factor of 3 when an optimal concentration was reached as predicted for susceptibility matching by combining intrinsic susceptibilities of tissue, blood, and gas.

Purpose To determine the reproducibility of several parameters of the ADC measurement by calculating the scan-to-scan intrasubject variability. Materials and Methods Measurements were performed using a gradient-echo sequence with a bipolar gradient for diffusion weighting (b = 3.89 sec/cm2). Five patients with pulmonary emphysema, and six healthy-lung volunteers were included in the study. Images were acquired after inspiration of 3He during a single inspiratory breath-hold. To assess the reproducibility, the measurement was performed twice (time between measurements = 20 minutes) without repositioning the subjects. Analysis was performed on the basis of region-of-interest (ROI) analysis and global lung ADC histograms. Results The mean ADC of a ROI varied by 5.1% between two measurements for volunteers and by 6.1% for patients. In the global evaluation, the 75th percentile demonstrated the best reproducibility (2%), while other parameters showed variations up to 12%. Only the variation of the standard deviation (SD) and the measure of homogeneity of the ADC map showed a significant difference between patients and volunteers. Conclusion Diffusion-weighted imaging (DWI) is a well-reproducible method for assessing the lung microstructure. J. Magn. Reson. Imaging 2005;21:765–774. © 2005 Wiley-Liss, Inc.

Rationale and objectives To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. Materials and methods We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. Results Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. Conclusion There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.

Lung imaging has traditionally relied on x-ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment.

Purpose: To compare the spatial correlation of ventilation surrogates computed from inspiratory and expiratory breath-hold CT with hyperpolarized Helium-3 & Xenon-129 MRI in a cohort of lung cancer patients. Methods: 5 patients underwent expiration & inspiration breath-hold CT. Xenon-129 & 1H MRI were also acquired at the same inflation state as inspiratory CT. This was followed immediately by acquisition of Helium-3 & 1H MRI in the same breath and at the same inflation state as inspiratory CT. Expiration CT was deformably registered to inspiration CT for calculation of ventilation CT from voxel-wise differences in Hounsfield units. Inspiration CT and the Xenon-129's corresponding anatomical 1H MRI were registered to Helium-3 MRI via the same-breath anatomical 1H MRI. This enabled direct comparison of CT ventilation with Helium-3 MRI & Xenon-129 MRI for the median values in corresponding regions of interest, ranging from finer to coarser in-plane dimensions of 10 by 10, 20 by 20, 30 by 30 and 40 by 40, located within the lungs as defined by the same-breath 1H MRI lung mask. Spearman coefficients were used to assess voxel-level correlation. Results: The median Spearman's coefficients of ventilation CT with Helium-3 & Xenon-129 MRI for ROIs of 10 by 10, 20 by 20, 30 by 30 and 40 by 40 were 0.52, 0.56, 0.60 and 0.68 and 0.40, 0.42, 0.52 and 0.70, respectively. Conclusion: This work demonstrates a method of acquiring CT & hyperpolarized gas MRI (Helium-3 & Xenon-129 MRI) in similar breath-holds to enable direct spatial comparison of ventilation maps. Initial results show moderate correlation between ventilation CT & hyperpolarized gas MRI, improving for coarser regions which could be attributable to the inherent noise in CT intensity, non-ventilatory effects and registration errors at the voxel-level. Thus, it may be more beneficial to quantify ventilation at a more regional level.

Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases.We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge.Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test.Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV(1) (r = 0.71, P.002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV(1). The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P.02) and extent (P.02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure.HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.

Rationale and Objectives The authors tested the feasibility of a magnetic resonance (MR) imaging method combining the use of hyperpolarized helium 3 (3He) for ventilation imaging and an arterial spin-tagging sequence for perfusion imaging in six healthy human subjects. Materials and Methods High-resolution sagittal images depicting 3He distribution were acquired after the subjects' inhalation of 500 mL of laser-hyperpolarized 3He produced by spin-exchange optical pumping. Perfusion MR imaging was performed with a steady-state arterial spin-tagging sequence that enabled the acquisition of three-dimensional images of pulmonary perfusion without the need for subject breath holding. Results The 3He ventilation images display, with high signal intensity and detailed anatomic localization, the airspace of the lung parenchyma. The signal intensity on the perfusion images decreased by 23.2% with the use of arterial spin tagging. Ventilation and perfusion were matched, as is expected in healthy subjects. Conclusion This method may have important applications in the assessment of lung function, enabling the calculation of regional ventilation–perfusion ratios. It may also aid in the selection of candidates for lung volume-reduction surgery.

The nuclear spin polarization of the noble gas isotopes (3)He and (129)Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments.