Andrew Wheatley

Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation.

RATIONALE AND OBJECTIVES To improve intra- and interobserver variability and enable the use of functional magnetic resonance imaging (MRI) for multicenter, multiobserver studies, we generated a semiautomated segmentation method for hyperpolarized helium-3 ((3)He) MRI. Therefore the objective of this study was to compare the reproducibility and spatial agreement of manual and semiautomated segmentation of (3)He MRI ventilation defect volume (VDV) and ventilation volume (VV) in subjects with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). MATERIALS AND METHODS The multistep semiautomated segmentation method we developed employed hierarchical K-means clustering to classify (3)He MRI pixel intensity values into five user-determined clusters ranging from signal void to hyperintense. A seeded region-growing algorithm was also used to segment the (1)H MRI thoracic cavity for coregistration to the (3)He cluster-map, generating VDV and VV. RESULTS We compared manual segmentation performed by an expert observer and semiautomated measurements of (3)He MRI VDV and observed strong significant correlations between the volumes generated using each method (asthma, n = 5, r = 0.89, P < .0001; COPD, n = 5, r = 0.84, P < .0001; CF, n = 5, r = 0.89, P < .0001). Semiautomated VDV had high interobserver reproducibility (coefficient of variation [CV] = 7%, intraclass correlation coefficient [ICC] = 0.96); intraobserver reproducibility was significantly higher for semiautomated (CV = 5%, ICC = 1.00) compared to manual VDV (CV = 12%, ICC = 0.98). Spatial agreement for VV determined using the Dice coefficient (D) was also high for all disease states (asthma, D = 0.95; COPD, D = 0.88; CF, D = 0.90). CONCLUSIONS Semiautomated segmentation (3)He MRI provides excellent inter- and intraobserver precision with high spatial and quantitative agreement with manual measurements enabling its use in longitudinal studies.

Hyperpolarized 3He and 129Xe MR Imaging in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.

Chronic Obstructive Pulmonary Disease: Longitudinal Hyperpolarized 3He MR Imaging

PURPOSE To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. MATERIALS AND METHODS All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and age range) at baseline and 26 months +/- 2 (standard deviation) later. Apparent diffusion coefficients (ADCs) derived from (3)He MR imaging were calculated from diffusion-weighted (3)He MR images, and (3)He ventilation defect volume (VDV) and ventilation defect percentage (VDP) were generated after manual segmentation of (3)He MR spin-density images. RESULTS For subjects with COPD, significant increases in (3)He MR imaging-derived VDV (P = .03), VDP (P = .006), and ADC (P = .02) were detected, whereas there was no significant change in forced expiratory volume in 1 second (FEV(1)) (P = .97). For healthy never-smokers, there was no significant change in imaging or pulmonary function measurements at follow-up. There was a significant correlation between changes in FEV(1) and changes in VDV (r = -0.70, P = .02) and VDP (r = -0.70, P = .03). CONCLUSION For this small pilot group of ex-smokers with COPD, (3)He MR imaging-derived VDV, VDP, and ADC measurements worsened significantly, but there was no significant change in FEV(1), suggesting increased sensitivity of hyperpolarized (3)He MR imaging for depicting COPD changes during short time periods.

Fast retrospectively gated quantitative four-dimensional (4D) cardiac micro computed tomography imaging of free-breathing mice

Objective:We sought to demonstrate retrospectively gated dynamic 3D cardiac micro computed tomography (CT) of free-breathing mice. Materials and Methods:Five C57Bl6 mice were scanned using a cone-beam scanner with a slip-ring-mounted flat-panel detector. After the injection of an intravascular iodinated contrast agent, projection images were acquired over the course of 50 seconds, while the scanner rotated through 10 complete rotations. The mouse respiratory and electrocardiogram signals were recorder simultaneously with image acquisition. After acquisition, the projection images were retrospectively sorted into projections belonging to different cardiac time points, occurring only during expiration. Results:Dynamic 3D cardiac images, with isotropic 150-&mgr;m voxel spacing, were reconstructed at 12-millisecond intervals throughout the cardiac cycle in all mice. The average ejection fraction and cardiac output were 58.2 ± 4.6% and 11.4 ± 1.3 mL/min, respectively. The measured entrance dose for the entire scan was 28 cGy. Repeat scans of the same animals showed that intrasubject variability was smaller than intersubject variability. Conclusions:We have developed a high-resolution micro computed tomography method for evaluating the cardiac function and morphology of free-breathing mice in acquisition times shorter than 1 minute.

Hyperpolarized 3He and 129Xe MRI: Differences in asthma before bronchodilation

To compare hyperpolarized helium‐3 (3He) and xenon‐129 (129Xe) MRI in asthmatics before and after salbutamol inhalation.

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 ((3)He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for (3)He 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, (1)H MRI and hyperpolarized (3)He MRI at 3.0T. (3)He ventilation defect percent (VDP) was generated from (3)He static ventilation images and (1)H thoracic images and the (3)He 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 (3)He 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 (3)He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.

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.

Detection of longitudinal lung structural and functional changes after diagnosis of radiation-induced lung injury using hyperpolarized 3He magnetic resonance imaging.

PURPOSE Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation-induced lung injury (RILI) still occurs in over 1/3 of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized 3He magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post-RILI. METHODS All subjects underwent spirometry, plethysmography, and MRI at 3.0 T 35.1 +/- 12.2 weeks after radiation therapy commenced. Thoracic 1H, static 3He ventilation, and 3He diffusion-weighted images were acquired to generate the 3He apparent diffusion coefficient (ADC) and 3He percent ventilated volume (PVV). Four subjects returned 22.0 +/- 0.8 weeks after baseline imaging for follow-up spirometry and 3He MRI measurements of ADC and PVV. RESULTS At baseline, PVV was significantly different (p = 0.025) and lower in the ipsilateral diseased lung (55 +/- 29%) compared to the contralateral nondiseased lung (88 +/- 5%). Longitudinally, significant increases were observed for 3He MRI PVV (16% +/- 6%, p = 0.012) and 3He MRI ADC (0.02 +/- 0.01 cm2/s, p = 0.003) in the contralateral lung only, in the four subjects who returned for follow-up, while no changes in the ipsilateral lung were reported. CONCLUSIONS Hyperpolarized 3He MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation-induced injury.

On the role of abnormal DL CO in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI

Background The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. Objective We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. Methods We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St Georges Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 (3He) MRI. The 6MWT distance (6MWD), SGRQ scores, 3He MRI apparent diffusion coefficients (ADC) and CT attenuation values below −950 HU (RA950) were evaluated. Results Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for 3He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=−0.51, p=0.0002). Conclusions In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and 3He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised 3He MRI in ex-smokers without COPD.

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.