Hyperpolarized Helium-3 Magnetic Resonance Imaging Research Articles

Ventilation defects on hyperpolarized helium-3 MRI in asthma are predictive of 2-year exacerbation frequency

There is an unmet need for an objective biomarker to predict asthma exacerbations. Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging. Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations. A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n= 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n= 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI= 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response. VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations.

Semiautomated Ventilation Defect Quantification in Exercise-induced Bronchoconstriction Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: A Repeatability Study

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). 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. 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. 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.

Assessment of Repeatability of Hyperpolarized Gas MR Ventilation Functional Imaging in Cystic Fibrosis

Hyperpolarized (HP) gas magnetic resonance imaging (MRI) is an advanced imaging technique that provides high-resolution regional information on lung function without using ionizing radiation. Before this modality can be considered for assessing clinical or investigational interventions, baseline repeatability needs to be established. We assessed repeatability of lung function measurement using HP helium-3 MRI (HP (3)He MRI) in a small cohort of patients with cystic fibrosis (CF). We examined repeatability of HP (3)He MR images of five patients with CF in four scanning sessions over a 4-week period. We acquired images on a Philips 3.0Tesla Achieva MRI scanner using a quadrature, flexible, wrap-around, (3)He radiofrequency coil with a fast gradient-echo pulse sequence. We determined ventilation volume and ventilation defect volume using an advanced semiautomatic segmentation algorithm and also quantified ventilation heterogeneity. There were no significant differences in total ventilation volume, ventilation defect volume, ventilation defect percentage, or mean ventilation heterogeneity (repeated-measures analysis of variance, P=.2116, P=.2825, P=.2871, and P=.7265, respectively) in the patients across the four scanning sessions. Our results indicate that total ventilation volume, ventilation defect volume, ventilation defect percentage, and mean ventilation heterogeneity as assessed by HP gas MRI in CF patients with stable health are reproducible over time. This repeatability and the technique's capability to provide noninvasive high-resolution data on regional lung function without ionizing radiation make (3)He MRI a potentially useful outcome measure for CF-related clinical trials.

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

Markers of Vascular Perturbation Correlate with Airway Structural Change in Asthma

Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than -856 Hounsfield units [HU] at functional residual capacity and -950 HU at total lung capacity [TLC]). VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than -950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities.

Semiautomatic Segmentation of Ventilated Airspaces in Healthy and Asthmatic Subjects Using HyperpolarizedHeMRI

A segmentation algorithm to isolate areas of ventilation from hyperpolarized helium-3 magnetic resonance imaging (HP 3He MRI) is described. The algorithm was tested with HP 3He MRI data from four healthy and six asthmatic subjects. Ventilated lung volume (VLV) measured using our semiautomated technique was compared to that obtained from manual outlining of ventilated lung regions and to standard spirometric measurements. VLVs from both approaches were highly correlated (R = 0.99; P < 0.0001) with a mean difference of 3.8 mL and 95% agreement indices of −30.8 mL and 38.4 mL. There was no significant difference between the VLVs obtained through the semiautomatic approach and the manual approach. A Dice coefficient which quantified the intersection of the two datasets was calculated and ranged from 0.95 to 0.97 with a mean of 0.96 ± 0.01 (mean ± SD). VLVs obtained through the semiautomatic algorithm were also highly correlated with measurements of forced expiratory volume in one second (FEV1) (R = 0.82; P = 0.0035) and forced vital capacity (FVC) (R = 0.95; P < 0.0001). The technique may open new pathways toward advancing more quantitative characterization of ventilation for routine clinical assessment for asthma severity as well as a number of other respiratory diseases.

Pulmonary ventilation visualized using hyperpolarized helium-3 and xenon-129 magnetic resonance imaging: differences in COPD and relationship to emphysema

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 ((129)Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 ((3)He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized (3)He and (129)Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between (3)He and (129)Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. (3)He and (129)Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by (3)He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by (3)He gas only, mean (3)He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm(2)/s, ADCHX = 0.470 ± 0.125 cm(2)/s, P < 0.0001). The difference between (3)He and (129)Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and (3)He ADCHO (r = 0.70, P = 0.02), but not CT wall area percentage (r = -0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased (129)Xe MRI ventilation compared with (3)He MRI, and these regions of decreased (129)Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.

Evaluating bronchodilator effects in chronic obstructive pulmonary disease using diffusion-weighted hyperpolarized helium-3 magnetic resonance imaging

The objective of this study was to evaluate the regional effects of bronchodilator administration in chronic obstructive pulmonary disease (COPD) using hyperpolarized helium-3 ((3)He) MRI apparent diffusion coefficient (ADC). Ten COPD ex-smokers provided written, informed consent and underwent diffusion-weighted, hyperpolarized (3)He 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 (3)He signal at both time points, and mean ADC within those regions of interest (ROI) was determined for a measurement of previously ventilated ROI ADC (ADC(P)). Lung ROI with (3)He 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 (ADC(N)). Postsalbutamol, no significant differences were detected in WL ADC (P = 0.516). There were no significant differences between ADC(N) and ADC(P) postsalbutamol (P = 1.00), suggesting that the ADC(N) lung regions were not more emphysematous than the lung ROI participating in ventilation before bronchodilator administration. Postsalbutamol, a statistically significant decrease in ADC(P) (P = 0.01) was detected, and there were significant differences between ADC(P) 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 (3)He MRI ADC provides insights into lung alterations that accompany improvements in regional (3)He gas distribution after bronchodilator administration.

Quantitative Evaluation of Hyperpolarized Helium-3 Magnetic Resonance Imaging of Lung Function Variability in Cystic Fibrosis

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). 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). 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. 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.

Helical Tomotherapy Planning for Lung Cancer Based on Ventilation Magnetic Resonance Imaging

To investigate the feasibility of lung ventilation-based treatment planning, computed tomography and hyperpolarized (HP) helium-3 (He-3) magnetic resonance imaging (MRI) ventilation images of 6 subjects were coregistered for intensity-modulated radiation therapy planning in Tomotherapy. Highly-functional lungs (HFL) and less-functional lungs (LFL) were contoured based on their ventilation image intensities, and a cylindrical planning-target-volume was simulated at locations adjacent to both HFL and LFL. Annals of an anatomy-based plan (Plan 1) and a ventilation-based plan (Plan 2) were generated. The following dosimetric parameters were determined and compared between the 2 plans: percentage of total/HFL volume receiving ≥20 Gy, 15 Gy, 10 Gy, and 5 Gy (TLV 20, HFLV 20, TLV 15, HFLV 15, TLV 10, HFLV 10, TLV 5, HFLV 5), mean total/HFL dose (MTLD/HFLD), maximum doses to all organs at risk (OARs), and target dose conformality. Compared with Plan 1, Plan 2 reduced mean HFLD (mean reduction, 0.8 Gy), MTLD (mean reduction, 0.6 Gy), HFLV 20 (mean reduction, 1.9%), TLV 20 (mean reduction, 1.5%), TLV 15 (mean reduction, 1.7%), and TLV 10 (mean reduction, 2.1%). P-values of the above comparisons are less than 0.05 using the Wilcoxon signed rank test. For HFLV 15, HFLV 10, TLV 5, and HTLV 5, Plan 2 resulted in lower values than plan 1 but the differences are not significant ( P-value range, 0.063–0.219). Plan 2 did not significantly change maximum doses to OARs ( P-value range, 0.063–0.563) and target conformality ( P = 1.000). HP He-3 MRI of patients with lung disease shows a highly heterogeneous ventilation capacity that can be utilized for functional treatment planning. Moderate but statistically significant improvements in sparing functional lungs were achieved using helical tomotherapy plans.

Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging

Purpose To compare hyperpolarized helium-3 magnetic resonance imaging ( 3He-MRI) acquired from non-small cell lung cancer (NSCLC) patients before and after external beam radiotherapy (EBRT). Methods and materials In an Ethics Committee-approved prospective study, five patients with histologically confirmed NSCLC gave written informed consent to undergo computed tomography (CT) and 3He-MR ventilation imaging 1 week prior to and 3 months after radiotherapy. Images were registered to pre-treatment CT using anatomical landmark-based rigid registration to enable comparison. Emphysema was graded from examination of the CT. MRI-defined ventilation was calculated as the intersection of 3He-MRI and CT lung volume as a percentage of the CT lung volume for the whole lung and regions of CT-defined pneumonitis. Results On pre-treatment images, there was a significant correlation between the degree of CT-defined emphysema and 3He-MRI whole lung ventilation (Spearman’s rho = 0.90, p = 0.04). After radiation therapy, pneumonitis was evident on CT for 3/5 patients. For these cases, 3He-MRI ventilation was significantly reduced within the regions of pneumonitis (pre: 94.1 ± 2.2%, post: 73.7 ± 4.7%; matched pairs Student’s t-test, p = 0.02, mean difference = 20.4%, 95% confidence interval 6.3–34.6%). Conclusions This work demonstrates the feasibility of detecting ventilation changes between pre- and post-treatment using hyperpolarized helium-3 MRI for patients with NSCLC. Pre-treatment, the degree of emphysema and 3He-MRI ventilation were correlated. For three cases of radiation pneumonitis, 3He-MRI ventilation changes between pre- and post-treatment imaging were consistent with CT evidence of radiation-induced lung injury.

Hyperpolarized 3He magnetic resonance imaging-derived pulmonary pressure-volume curves

We aimed to evaluate the potential for the use of hyperpolarized helium-3 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) surrogates of alveolar size, together with literature-based morphological parameters in a theoretical model of lung mechanics to simulate noninvasive transpulmonary pressure-volume curves. Fourteen ex-smokers with chronic obstructive pulmonary disease (COPD) (n = 8 stage II, n = 6 stage III/IV COPD) and five age-matched never-smokers, provided written, informed consent and were evaluated at baseline and 26 + or - 2 mo later (n = 15 subjects) using plethysmography, spirometry, and (3)He MRI at 3.0 T. Total lung capacity, residual volume, and literature-based morphological parameters were used with alveolar volumes derived from (3)He ADC to simulate noninvasive pressure-volume curves. The resultant anterior-posterior transpulmonary pressure gradient was significantly decreased for stage II COPD (P < 0.01) and stage III COPD subjects (P < 0.001) compared with healthy volunteers. Both COPD subgroups showed increased alveolar radius compared with healthy subjects (P < 0.01, stage II COPD; P < 0.001, stage III COPD). In addition, surface area and surface tension were significantly increased in stage III COPD compared with healthy volunteers (P < 0.01). These results suggest that (3)He MRI provides a potential noninvasive approach to evaluate lung mechanics regionally and further supports the use of ADC values as a regional noninvasive probe of pulmonary microstructure and compliance.

Hyperpolarized 3He magnetic resonance imaging: Preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease

Rationale and objectives Emphysema and small airway obstruction are the pathological hallmarks of chronic obstructive pulmonary disease (COPD). The aim of this pilot study in a small group of chronic obstructive pulmonary disease (COPD) patients was to quantify hyperpolarized helium-3 ( 3He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for 3He MRI in detecting the lung structural and functional COPD phenotypes. Materials and methods We evaluated 20 ex-smokers with stage I ( n = 1), stage II ( n = 9) and stage III COPD ( n = 10). All subjects underwent same-day plethysmography, spirometry, 1H MRI and hyperpolarized 3He MRI at 3.0 T. 3He ventilation defect percent (VDP) was generated from 3He static ventilation images and 1H thoracic images and the 3He apparent diffusion coefficient (ADC) was derived from diffusion-weighted MRI. Results Based on the relative contribution of normalized ADC and VDP, there was evidence of a predominant 3He MRI measurement in seven patients ( n = 3 mainly ventilation defects or VDP dominant (VD), n = 4 mainly increased ADC or ADC dominant (AD)). Analysis of variance (ANOVA) showed significantly lower ADC for subjects with predominantly elevated VDP ( p = 0.02 compared to subjects with predominantly elevated ADC; p = 0.008 compared to mixed group) and significantly decreased VDP for subjects with predominantly elevated ADC ( p = 0.003, compared to mixed group). Conclusion In this small pilot study, a preliminary analysis shows the potential for 3He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.

Sci-Thurs AM: YIS-06: Longitudinal Hyperpolarized 3He Magnetic Resonance Imaging of Chronic Obstructive Pulmonary Disease

RATIONALE: To date, no studies have quantitatively evaluated chronic obstructive pulmonary disease (COPD) longitudinally using hyperpolarized helium-3 () magnetic resonance imaging (MRI). OBJECTIVES: To evaluate COPD longitudinally using hyperpolarized MRI and to determine correlations between the changes in MRI ventilation defect volume (VDV), apparent diffusion coefficients (ADC) and changes in pulmonary function. METHODS: Hyperpolarized MRI, spirometry and plethysmography were performed in 15 COPD ex-smokers ( stage II and stage III/IV COPD) at baseline and 26±2 months later. MRI ADC values were calculated from MRI diffusion-weighted images and VDV were generated after manual segmentation of MRI spin-density images. MEASUREMENTS AND MAIN RESULTS: At follow-up, COPD subjects showed significant increases in MRI CS VDV (), WL VDV (), as well as ADC () and no significant change in (). There was a significant correlation between changes in and changes in CS VDV (, ), however no significant correlations between smoking history (years non-smoker at baseline) and changes in MRI measurements or was found. CONCLUSIONS: For COPD ex-smokers, MRI VDV and ADC measurements worsened significantly but there was no significant change in FEV1, suggesting higher sensitivity of hyperpolarized MRI to COPD changes over short periods of time.

Functional image-based radiotherapy planning for non-small cell lung cancer: A simulation study

Background and purpose To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging ( 3He-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC). Material and methods Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung volume receiving ⩾20 Gy ( V 20), and the other to minimise only the functional lung volume receiving ⩾20 Gy ( FV 20). Dose–volume characteristics and a plan quality index related to planning target volume coverage by the 95% isodose ( V PTV95/ FV 20) were compared between anatomical and functional plans using the Wilcoxon signed ranks test. Results Compared to anatomical IMRT plans, functional planning reduced FV 20 (median 2.7%, range 0.6–3.5%, p = 0.02), and total lung V 20 (median 1.5%, 0.5–2.7%, p = 0.02), with a small reduction in mean functional lung dose (median 0.4 Gy, 0–0.7 Gy, p = 0.03). There were no significant differences in target volume coverage or organ-at-risk doses. Plan quality index was improved for functional plans (median increase 1.4, range 0–11.8, p = 0.02). Conclusions Statistically significant reductions in FV 20, V 20 and mean functional lung dose are possible when IMRT planning is supplemented by functional information derived from SPECT or 3He-MRI.

Hyperpolarized 3He MR Imaging of the Lung

To prospectively investigate the number, location, and size of ventilation defects and correlate these findings with pulmonary function tests (PFTs) when performing hyperpolarized helium-3 (HP 3He) magnetic resonance imaging (MRI) of the lung in healthy young adults. Six healthy adult female volunteers underwent standard PFT and MRI of the lungs after inhalation of HP 3He. HP 3He MR images were evaluated by 4 reviewers in consensus. Number, location, and size of ventilation defects were recorded. Locations of ventilation defects included the right upper lobe, right middle lobe, right lower lobe, left upper lobe, left lower lobe, and lingula. Ventilation defects were localized into central, middle, or peripheral portions of the lungs. Size of ventilation defects was categorized with a maximum diameter of either <or=3 cm or >3 cm. HP 3He MRI findings were correlated with PFT results. The study cohort comprised 6 healthy, young adult female volunteers (mean age 22.5 y, range: 20-25 y) who underwent both PFT and HP 3He MRI. Five (83.3%) out of 6 volunteers had at least 1 ventilation defect (mean=2.3; range: 1-4; 95% confidence interval: 1.3-3.8 defects/patient). Among a total of 14 ventilation defects observed from 5 healthy, young adult volunteers, ventilation defects were observed in left lower lobe in 6 (42.9%), right lower lobe in 3 (21.4%), right upper lobe in 3 (21.4%), and left upper lobe in 2 (14.3%) patients. No ventilation defects were observed in the right middle lobe and lingula. All observed ventilation defects were less than 3 cm in size and peripherally located. There was no correlation between number, location, or size of ventilation defects and PFT results. Small (<or=3 cm) peripherally located ventilation defects can be seen in the majority of healthy, young adult volunteers, and should not be mistaken as abnormalities when evaluating HP 3He MRI. These ventilation defects are located in the peripheral upper lobes and lower lobes (lower lobes>upper lobes) while sparing right middle lobe and lingula. The number, location, and size of ventilation defects on HP 3He MRI were not correlated with PFT results in the normal range, which suggests HP 3He MRI may be more sensitive than PFT for evaluating small ventilation defects in young adults.

Rapid Prototyping Raw Models on the Basis of High Resolution Computed Tomography Lung Data for Respiratory Flow Dynamics

Three-dimensional image reconstruction by volume rendering and rapid prototyping has made it possible to visualize anatomic structures in three dimensions for interventional planning and academic research. Volumetric chest computed tomography was performed on a healthy volunteer. Computed tomographic images of the larger bronchial branches were segmented by an extended three-dimensional region-growing algorithm, converted into a stereolithography file, and used for computer-aided design on a laser sintering machine. The injection of gases for respiratory flow modeling and measurements using magnetic resonance imaging were done on a hollow cast. Manufacturing the rapid prototype took about 40 minutes and included the airway tree from trackea to segmental bronchi (fifth generation). The branching of the airways are clearly visible in the (3)He images, and the radial imaging has the potential to elucidate the airway dimensions. The results for flow patterns in the human bronchial tree using the rapid-prototype model with hyperpolarized helium-3 magnetic resonance imaging show the value of this model for flow phantom studies.

An image acquisition and registration strategy for the fusion of hyperpolarized helium-3 MRI and x-ray CT images of the lung

The purpose of this ethics committee approved prospective study was to evaluate an image acquisition and registration protocol for hyperpolarized helium-3 magnetic resonance imaging (3He-MRI) and x-ray computed tomography. Nine patients with non-small cell lung cancer (NSCLC) gave written informed consent to undergo a free-breathing CT, an inspiration breath-hold CT and a 3D ventilation 3He-MRI in CT position using an elliptical birdcage radiofrequency (RF) body coil. 3He-MRI to CT image fusion was performed using a rigid registration algorithm which was assessed by two observers using anatomical landmarks and a percentage volume overlap coefficient. Registration of 3He-MRI to breath-hold CT was more accurate than to free-breathing CT; overlap 82.9 ± 4.2% versus 59.8 ± 9.0% (p < 0.001) and mean landmark error 0.75 ± 0.24 cm versus 1.25 ± 0.60 cm (p = 0.002). Image registration is significantly improved by using an imaging protocol that enables both 3He-MRI and CT to be acquired with similar breath holds and body position through the use of a birdcage 3He-MRI body RF coil and an inspiration breath-hold CT. Fusion of 3He-MRI to CT may be useful for the assessment of patients with lung diseases.

Feasibility of Image Registration and Intensity-Modulated Radiotherapy Planning With Hyperpolarized Helium-3 Magnetic Resonance Imaging for Non–Small-Cell Lung Cancer

Purpose: To demonstrate the feasibility of registering hyperpolarized helium-3 magnetic resonance images (3He-MRI) to X-ray computed tomography (CT) for functionally weighted intensity-modulated radiotherapy (IMRT) planning.Methods and Materials: Six patients with non–small-cell lung cancer underwent 3He ventilation MRI, which was fused with radiotherapy planning CT using rigid registration. Registration accuracy was assessed using an overlap coefficient, calculated as the proportion of the segmented 3He-MR volume (VMRI) that intersects the segmented CT lung volume expressed as a percentage of VMRI. For each patient, an IMRT plan that minimized the volume of total lung receiving a dose ≥20 Gy (V20) was compared with a plan that minimized the V20 to well-ventilated lung defined by the registered 3He-MRI.Results: The 3He-MRI and CT were registered with sufficient accuracy to enable functionally guided IMRT planning (median overlap, 89%; range, 72–97%). In comparison with the total lung IMRT plans, IMRT constrained with 3He-MRI reduced the V20 not only for the well-ventilated lung (median reduction, 3.1%; range, 0.4–5.1%; p = 0.028) but also for the total lung volume (median reduction, 1.6%; range, 0.2–3.7%; p = 0.028).Conclusions: Statistically significant improvements to IMRT plans are possible using functional information provided by 3He-MRI that has been registered to radiotherapy planning CT.

The variability of regional airflow obstruction within the lungs of patients with asthma: Assessment with hyperpolarized helium-3 magnetic resonance imaging

It is unknown whether focal changes of airflow obstruction within the lungs of patients with asthma vary or are fixed in location with time or repeated bronchoconstriction. With hyperpolarized helium-3 magnetic resonance (H(3)HeMR) imaging, the airspaces are depicted and focal areas of airflow obstruction are shown as "ventilation defects." To investigate the regional changes of airflow obstruction with time and repeated bronchoconstriction. H(3)HeMR and spirometry were performed before (pre) and immediately after (post) methacholine challenge in 10 young patients with asthma on 2 days that were 7-476 days (mean, 185.3 +/- 37.2 days) apart. Pair-wise image comparisons were performed to determine the change in location of ventilation defects within the lung and their change in size. When comparing premethacholine versus premethacholine and postmethacholine versus post-methacholine images of the 2 days, 41% +/- 10% and 69% +/- 5% (P = .017) of defects, respectively, were in the same location, and of those, 69% +/- 12% and 43% +/- 5% (P = .022), respectively, did not change size. Comparing premethacholine versus postmethacholine images, 58% +/- 9% of defects were in the same location on day 1 and 73% +/- 7% (P = .088) on day 2. On both days, the percent increase in defect number from premethacholine to postmethacholine was much greater than the percent decrease in spirometric values (P < .001). Many of the ventilation defects persisted or recurred in the same location with time or repeated bronchoconstriction, suggesting that the regional changes of airflow obstruction are relatively fixed within the lung. The findings give new insight into the regional airflow variability within the lungs of patients with asthma.