3He Magnetic Resonance Research Articles

Reduced Total Airway Count and Airway Wall Tapering after Three-Years in Ex-Smokers

Computed tomography (CT) total-airway-count (TAC) and airway wall-thickness differ across chronic obstructive pulmonary disease (COPD) severities, but longitudinal insights are lacking. The aim of this study was to evaluate longitudinal CT airway measurements over three-years in ex-smokers. In this prospective convenience sample study, ex-smokers with (n = 50; 13 female; age = 70 ± 9 years; pack-years = 43 ± 26) and without (n = 40; 17 female; age = 69 ± 10 years; pack-years = 31 ± 17) COPD completed CT, 3He magnetic resonance imaging (MRI), and pulmonary function tests at baseline and three-year follow-up. CT TAC, airway wall-area (WA), lumen-area (LA), and wall-area percent (WA%) were generated. Emphysema was quantified as the relative-area-of-the-lung with attenuation < –950 Hounsfield-units (RA950). MRI ventilation-defect-percent (VDP) was also quantified. Differences over time were evaluated using paired-samples t tests. Multivariable prediction models using the backwards approach were generated. After three-years, forced-expiratory-volume in 1-second (FEV1) was not different in ex-smokers with (p = 0.4) and without (p = 0.5) COPD, whereas RA950 was (p < 0.001, p = 0.02, respectively). In ex-smokers without COPD, there was no change in TAC (p = 0.2); however, LA (p = 0.009) and WA% (p = 0.01) were significantly different. In ex-smokers with COPD, TAC (p < 0.001), WA (p = 0.04), LA (p < 0.001), and WA% (p < 0.001) were significantly different. In all ex-smokers, TAC was related to VDP (baseline: ρ = –0.30, p = 0.005; follow-up: ρ = –0.33, p = 0.002). In significant multivariable models, baseline airway wall-thickness was predictive of TAC worsening. After three-years, in the absence of FEV1 worsening, TAC diminished only in ex-smokers with COPD and airway walls were thinner in all ex-smokers. These longitudinal findings suggest that the evaluation of CT airway remodeling may be a useful clinical tool for predicting disease progression and managing COPD. Clinical trial registration: www.clinicaltrials.gov NCT02279329

Functional Lung Avoidance for Individualized Radiation Therapy: Results of a Double-Masked, Randomized Controlled Trial

To determine whether functional lung avoidance based on 3He magnetic resonance imaging (MRI) improves quality of life (QOL) for patients undergoing concurrent chemoradiotherapy (CCRT) for advanced non-small cell lung cancer. Patients with stage III non-small cell lung cancer (or oligometastatic disease treated with curative intent) undergoing CCRT with at least a 10 pack-year smoking history were eligible. Patients underwent pretreatment 3He MRI to measure lung ventilation and had 2 radiation therapy (RT) plans created before randomization: a standard plan, which did not make use of the 3He MRI, and an avoidance plan, preferentially sparing well-ventilated lung. All participants were masked to assignment except the physicist responsible for exporting the selected plan. The primary end point was patient-reported QOL measured at 3-months post-RT by the FACT-L lung cancer subscale (LCS); secondary end points included other QOL metrics, toxicity, and survival outcomes. Target accrual was 64. Twenty-seven patients were randomized before the trial was closed due to slower-than-expected accrual, with 11 randomized to the standard arm and 16 to the avoidance arm. Baseline patient characteristics were well-balanced. At 3 months post-RT, the mean ± SD LCS scores were 17.4 ± 2.8 versus 17.3 ± 6.1 for the standard and avoidance arms, respectively (P = .485). A clinically meaningful, prespecified decline of ≥3 points in the LCS score was observed in 50% (4/8) in the standard arm and 33% (4/12) in the avoidance arm (P = .648). Two patients in each arm developed grade ≥2 radiation pneumonitis, with no grade ≥4 toxicities. Although this trial did not reach full accrual, QOL scores were very similar between arms. Due to the scarcity of 3He MRI, other, more commonly available methods to measure functional lung, such as 4-dimensional computed tomography ventilation mapping, may be considered in the assessment of functional lung avoidance RT, and a larger, multicenter approach would be needed to accrue sufficient patients to test such approaches.

Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis Lung Disease

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized 3He Magnetic Resonance Imaging

The purpose of this study was to assess the effectiveness of hyperpolarized helium-3 magnetic resonance (MR)-based imaging markers in predicting future forced expiratory volume in one second decline/chronic obstructive pulmonary disorder progression in smokers compared to current diagnostic techniques. Total 60 subjects (15 nonsmokers and 45 smokers) participated in both baseline and follow-up visits (∼1.4years apart). At both visits, subjects completed pulmonary function testing, a six-minute walk test , and the St. George Respiratory Questionnaire. Using helium-3 MR imaging, means (M) and standard deviations (H) of oxygen tension (PAO2), fractional ventilation, and apparent diffusion coefficient were calculated across 12 regions of interest in the lungs. Subjects who experienced FEV1 decline >100mL/year were deemed "decliners," while those who did not were deemed "sustainers." Nonimaging and imaging prediction models were generated through a logistic regression model, which utilized measurements from sustainers and decliners. The nonimaging prediction model included the St. George Respiratory Questionnaire total score, diffusing capacity of carbon monoxide by the alveolar volume (DLCO/VA), and distance walked in a six-minute walk test. A receiving operating character curve for this model yielded a sensitivity of 75% and specificity of 68% with an overall area under the curve of 65%. The imaging prediction model generated following the same methodology included ADCH, FVH, and PAO2H. The resulting receiving operating character curve yielded a sensitivity of 87.5%, specificity of 82.8%, and an area under the curve of 89.7%. The imaging predication model generated from measurements obtained during 3He MR imaging is better able to predict future FEV1 decline compared to one based on current clinical tests and demographics. The imaging model's superiority appears to arise from its ability to distinguish well-circumscribed, severe disease from a more uniform distribution of moderately altered lung function, which is more closely associated with subsequent FEV1 decline.

Oscillometry and pulmonary MRI measurements of ventilation heterogeneity in obstructive lung disease: relationship to quality of life and disease control.

Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized 3He magnetic resonance imaging (MRI) and determined their relationships with quality of life scores and disease control/exacerbations. We also coregistered MRI ventilation maps to a computational airway tree model to generate patient-specific respiratory impedance predictions for comparison with experimental measurements. In COPD and asthma patients, respectively, forced oscillation technique (FOT)-derived peripheral resistance (5-19 Hz) and MRI ventilation defect percentage (VDP) were significantly related to quality of life (FOT: COPD ρ = 0.4, P = 0.004; asthma ρ = -0.3, P = 0.04; VDP: COPD ρ = 0.6, P = 0.003; asthma ρ = -0.3, P = 0.04). Patients with poorly controlled asthma (Asthmatic Control Questionnaire >2) had significantly increased resistance (5 Hz: P = 0.01; 5-19 Hz: P = 0.006) and reactance (5 Hz: P = 0.03). FOT-derived peripheral resistance (5-19 Hz) was significantly related to VDP in patients with asthma and COPD patients (asthma: ρ = 0.5, P < 0.001; COPD: ρ = 0.5, P = 0.01), whereas total respiratory impedance was related to VDP only in patients with asthma (resistance 5 Hz: ρ = 0.3, P = 0.02; reactance 5 Hz: ρ = -0.5, P < 0.001). Model-predicted and FOT-measured reactance (5 Hz) were correlated in patients with asthma (ρ = 0.5, P = 0.001), whereas in COPD patients, model-predicted and FOT-measured resistance (5-19 Hz) were correlated (ρ = 0.5, P = 0.004). In summary, in patients with asthma and COPD patients, we observed significant, independent relationships for FOT-measured impedance and MRI ventilation heterogeneity measurements with one another and with quality of life scores. NEW & NOTEWORTHY In 100 patients, including patients with asthma and ex-smokers, 3He MRI ventilation heterogeneity and respiratory system impedance were correlated and both were independently related to quality of life scores and asthma control. These findings demonstrated the critical relationships between respiratory system impedance and ventilation heterogeneity and their role in determining quality of life and disease control. These observations underscore the dominant role that abnormalities in the lung periphery play in ventilation heterogeneity that results in patients' symptoms.

Free-breathing Pulmonary MR Imaging to Quantify Regional Ventilation.

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.

Regional Heterogeneity of Lobar Ventilation in Asthma Using Hyperpolarized Helium-3 MRI

To determine lobar ventilation patterns in asthmatic lungs with hyperpolarized 3He magnetic resonance imaging (HP 3He MRI). 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. 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). 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.

Pulmonary 3He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency

Thoracic x-ray computed tomography (CT) and hyperpolarized 3He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (Lm) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers. We enrolled patients with AATD (n = 8; 57 ± 7 years), ex-smokers with COPD (n = 8; 77 ± 6 years), and a control group of never-smokers (n = 5; 64 ± 2 years) who underwent thoracic CT, MRI, spirometry, plethysmography, the St. George's Respiratory Questionnaire, and the 6-minute walk test during a single 2-hour visit. MRI-derived ADC, Lm, surface-to-volume ratio, and ventilation defect percent were generated for the apical, basal, and whole lung as was CT lung area ≤-950 Hounsfield units (RA950), low attenuating clusters, and airway count. In patients with AATD, there was a significantly different MRI-derived ADC (P = .03), Lm (P < .0001), and surface-to-volume ratio (P < .0001), but not diffusing capacity of carbon monoxide, residual volume or total lung capacity, or CT RA950 (P > .05) compared to COPD ex-smokers with a significantly different St. George's Respiratory Questionnaire. In this proof-of-concept demonstration, we evaluated CT and MRI lung emphysema measurements and observed significantly worse MRI biomarkers of emphysema in patients with AATD compared to patients with COPD, although CT RA950 and diffusing capacity of carbon monoxide were not significantly different, underscoring the sensitivity of MRI measurements of AATD emphysema.

Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis

BackgroundThis pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)–defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. MethodsPart 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). ResultsMean 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. ConclusionsTVD responded to ivacaftor therapy. 3He-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

Regional Heterogeneity of Chronic Obstructive Pulmonary Disease Phenotypes: Pulmonary 3He Magnetic Resonance Imaging and Computed Tomography

Pulmonary ventilation may be visualized and measured using hyperpolarized 3He magnetic resonance imaging (MRI) while emphysema and its distribution can be quantified using thoracic computed tomography (CT). Our objective was to phenotype ex-smokers with COPD based on the apical-to-basal distribution of ventilation abnormalities and emphysema to better understand how these phenotypes change regionally as COPD progresses. We evaluated 100 COPD ex-smokers who provided written informed consent and underwent spirometry, CT and 3He MRI. 3He MRI ventilation imaging was used to quantify the ventilation defect percent (VDP) for whole-lung and individual lung lobes. Regional VDP was used to generate the apical-lung (AL)-to-basal-lung (BL) difference (ΔVDP); a positive ΔVDP indicated AL-predominant and negative ΔVDP indicated BL-predominant ventilation defects. Emphysema was quantified using the relative-area-of-the-lung ≤−950HU (RA950) of the CT density histogram for whole-lung and individual lung lobes. The AL-to-BL RA950 difference (ΔRA950) was generated with a positive ΔRA950 indicating AL-predominant emphysema and a negative ΔRA950 indicating BL-predominant emphysema. Seventy-two ex-smokers reported BL-predominant MRI ventilation defects and 71 reported AL-predominant CT emphysema. BL-predominant ventilation defects (AL/BL: GOLD I = 18%/82%, GOLD II = 24%/76%) and AL-predominant emphysema (AL/BL: GOLD I = 84%/16%, GOLD II = 72%/28%) were the major phenotypes in mild-moderate COPD. In severe COPD there was a more uniform distribution for ventilation defects (AL/BL: GOLD III = 40%/60%, GOLD IV = 43%/57%) and emphysema (AL/BL: GOLD III = 64%/36%, GOLD IV = 43%/57%). Basal-lung ventilation defects predominated in mild-moderate GOLD grades, and a more homogeneous distribution of ventilation defects was observed in more advanced grade COPD; these differences suggest that over time, regional ventilation abnormalities become more homogenously distributed during disease progression.

Oscillatory Positive Expiratory Pressure in Chronic Obstructive Pulmonary Disease

Evidence-based guidance for the use of airway clearance techniques (ACT) in chronic obstructive pulmonary disease (COPD) is lacking in-part because well-established measurements of pulmonary function such as the forced expiratory volume in 1s (FEV1) are relatively insensitive to ACT. The objective of this crossover study was to evaluate daily use of an oscillatory positive expiratory pressure (oPEP) device for 21–28 days in COPD patients who were self-identified as sputum-producers or non-sputum-producers.COPD volunteers provided written informed consent to daily oPEP use in a randomized crossover fashion. Participants completed baseline, crossover and study-end pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ), Patient Evaluation Questionnaire (PEQ), Six-Minute Walk Test and 3He magnetic resonance imaging (MRI) for the measurement of ventilation abnormalities using the ventilation defect percent (VDP).Fourteen COPD patients, self-identified as sputum-producers and 13 COPD-non-sputum-producers completed the study. Post-oPEP, the PEQ-ease-bringing-up-sputum was improved for sputum-producers (p = 0.005) and non-sputum-producers (p = 0.04), the magnitude of which was greater for sputum-producers (p = 0.03). There were significant post-oPEP improvements for sputum-producers only for FVC (p = 0.01), 6MWD (p = 0.04), SGRQ total score (p = 0.01) as well as PEQ-patient-global-assessment (p = 0.02). Clinically relevant post-oPEP improvements for PEQ-ease-bringing-up-sputum/PEQ-patient-global-assessment/SGRQ/VDP were observed in 8/7/9/6 of 14 sputum-producers and 2/0/3/3 of 13 non-sputum-producers. The post-oPEP change in 3He MRI VDP was related to the change in PEQ-ease-bringing-up-sputum (r = 0.65, p = 0.0004) and FEV1 (r = –0.50, p = 0.009).In COPD patients with chronic sputum production, PEQ and SGRQ scores, FVC and 6MWD improved post-oPEP. FEV1 and PEQ-ease-bringing-up-sputum improvements were related to improved ventilation providing mechanistic evidence to support oPEP use in COPD. Clinical Trials # NCT02282189 and NCT02282202.

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never- and ex-smokers.

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.

Pulmonary Abnormalities and Carotid Atherosclerosis in Ex-Smokers without Airflow Limitation

It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 ± 6 years) and 27 ex-smokers (73 ± 9 years), who provided written informed consent to spirometry, plethysmography, 3He magnetic resonance imaging (MRI) and carotid ultrasound (US) and, for ex-smokers alone, thoracic X-ray computed tomography (CT). Ex-smokers had significantly greater 3He ventilation defect percent (VDP = 7%, p = 0.001) and carotid total plaque volume (TPV = 250 mm3, p = 0.002) than never-smokers, although there were no significant differences for spirometry or plethysmography, and CT airway and emphysema measurements were normal. There were univariate relationships for 3He VDP with carotid intima media thickness (IMT, r = 0.42, p = 0.004), TPV (r = 0.41, p = 0.006) and vessel wall volume (VWV, r = 0.40, p = 0.007). Multivariate models that included age, BMI, FEV1, DLCO and VDP showed that only VDP significantly predicted IMT (β = 0.41, p = 0.001), VWV (β = 0.45, p = 0.003) and TPV (β = 0.38, p = 0.005). In summary, there was imaging evidence of mild airways disease and carotid plaque burden that were related and significantly greater in ex-smokers without airflow limitation than in never-smokers.

Reply: On the Use of 3He Diffusion Magnetic Resonance as Evidence of Neo-Alveolarization during Childhood and Adolescence

Reply: On the Use of ³He Diffusion Magnetic Resonance as Evidence of Neo-Alveolarization during Childhood and Adolescence

It's about numbers, not pictures

the article in the current issue by Horn and colleagues ([4][1]) from Sheffield presents a significant change in the manner in which MRI in the lung using hyperpolarized gas (3He in this case, but also potentially 129Xe) is used. Since its inception, hyperpolarized gas imaging has shown an ability

Effect of Lung Inflation Level on Hyperpolarized3He Apparent Diffusion Coefficient Measurements in Never-Smokers

To evaluate the effects of lung volume differences on apparent diffusion coefficient (ADC) measurements on a regional basis, with breath holds at volumes adjusted for differences in lung size across individuals according to the subject's vital capacity (VC). This study was approved by the local institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Imaging was performed under a physician's Investigational New Drug application from the Food and Drug Administration. ADC changes as a function of inflation levels were evaluated in 24 healthy never-smokers across three lung volumes (20%, 60%, and 100% VC) on the basis of the spirometric data collected from each subject. Response variables based on lung volume and anatomic position were assessed with multifactorial analysis of variance followed by posthoc pair-wise testing. Imaging was performed with a 1.5-T magnetic resonance (MR) unit with use of a two-dimensional gradient-echo fast low-angle shot sequence. Significant differences in ADCs between lung volumes were observed for all inflation levels (20%, 60%, and 100% VC; P < .001), along with significant dependent-nondependent vertical gradients at 20% VC (P < .0001) and 60% VC (P < .0001, left lung only). In addition, significant differences between mean values in the left and right lungs with respect to those in the whole lung were observed at the lower lung inflation levels (20% and 60% VC, P < .01), reaching more uniform expansion at 100% VC. The results confirm known anatomic differences in patterns of regional inflation and ventilation with corresponding lung volume changes, emphasizing the need for tight control over lung volume when performing hyperpolarized helium 3 ((3)He) lung studies if (3)He MR imaging is to be used to follow up small longitudinal changes in lung abnormalities.

Pulmonary 3He magnetic resonance imaging of childhood asthma

Magnetic resonance imaging (MRI) with (3)He does not require ionizing radiation and has been shown to detect regional abnormalities in lung ventilation and structure in adults with asthma, but the method has not been extended to children with asthma. Measurements of regional lung ventilation and microstructure in subjects with childhood asthma could advance our understanding of disease mechanisms. We sought to determine whether (3)He MRI in children can identify abnormalities related to the diagnosis of asthma or prior history of respiratory illness. Forty-four children aged 9 to 10 years were recruited from a birth cohort at increased risk of asthma and allergic diseases. For each subject, a time-resolved 3-dimensional image series and a 3-dimensional diffusion-weighted image were acquired in separate breathing maneuvers. The numbers and sizes of ventilation defects were scored, and regional maps and statistics of average (3)He diffusion lengths were calculated. Children with mild-to-moderate asthma had lower average root-mean-square diffusion length (X(rms)) values (P = .004), increased regional SD of diffusion length values (P = .03), and higher defect scores (P = .03) than those without asthma. Children with histories of wheezing illness with rhinovirus infection before the third birthday had lower X(rms) values (P = .01) and higher defect scores (P = .05). MRI with (3)He detected more and larger regions of ventilation defect and a greater degree of restricted gas diffusion in children with asthma compared with those seen in children without asthma. These measures are consistent with regional obstruction and smaller and more regionally variable dimensions of the peripheral airways and alveolar spaces.

“Ventilatory alternans”: A left–right alternation of inspiratory airflow in humans

In a study visualizing ventilation with hyperpolarized 3He magnetic resonance imaging (MRI) in elite breath hold divers, the dynamic MRI images in one subject exhibited an apparent alternation of the image intensity between left and right lung. We hypothesized that the alternation resulted from alternating variations in inspiratory flow rate to left and right lungs. Analysis showed that the alternation was not due to random uncorrelated temporal fluctuations of intensity (p<0.001). The frequency of alternation was approximately 56min−1, suggesting a cardiac origin. Similar alternation of ventilation was confirmed retrospectively in 4 of 6 additional subjects. These observations are consistent with previous studies showing cardiogenic mixing of gas in the lung. We speculate that cardiogenic pendelluft, possibly from ballistic lateral motion of the beating heart, could cause alternating variations of inspiratory flow to the lungs.

Hyperpolarized 3He Magnetic Resonance Imaging: Comparison with Four-dimensional X-ray Computed Tomography Imaging in Lung Cancer

Pulmonary functional imaging using four-dimensional x-ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic resonance imaging (MRI) provides regional lung function estimates in patients with lung cancer in whom pulmonary function measurements are typically dominated by tumor burden. The aim of this study was to evaluate the quantitative spatial relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps. Eleven patients with lung cancer provided written informed consent to 4DCT imaging and MRI performed within 11 ± 14 days. Hyperpolarized (3)He MRI was acquired in breath-hold after inhalation from functional residual capacity of 1 L hyperpolarized (3)He, whereas 4DCT imaging was acquired over a single tidal breath of room air. For hyperpolarized (3)He MRI, the percentage ventilated volume was generated using semiautomated segmentation; for 4DCT imaging, pulmonary function maps were generated using the correspondence between identical tissue elements at inspiratory and expiratory phases to generate percentage ventilated volume. After accounting for differences in image acquisition lung volumes ((3)He MRI: 1.9 ± 0.5 L ipsilateral, 2.3 ± 0.7 L contralateral; 4DCT imaging: 1.2 ± 0.3 L ipsilateral, 1.3 ± 0.4 L contralateral), there was no significant difference in percentage ventilated volume between hyperpolarized (3)He MRI (72 ± 11% ipsilateral, 79 ± 12% contralateral) and 4DCT imaging (74 ± 3% ipsilateral, 75 ± 4% contralateral). Spatial correspondence between 4DCT and (3)He MRI ventilation was evaluated using the Dice similarity coefficient index (ipsilateral, 86± 12%; contralateral, 88 ± 12%). Despite rather large differences in image acquisition breathing maneuvers, good spatial and significant quantitative agreement was observed for ventilation maps on hyperpolarized (3)He MRI and 4DCT imaging, suggesting that pulmonary regions with good lung function are similar between modalities in this small group of patients with lung cancer.

Hyperpolarized3He and129Xe MR Imaging in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease

To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography. This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements. 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P<.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P<.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001). In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD.