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Ex-smokers without spirometry or CT evidence of chronic obstructive pulmonary disease (COPD) but with mildly abnormal diffusing capacity of the lungs for carbon monoxide (DL CO) are at higher risk of developing COPD. It remains difficult to make clinical management decisions for such ex-smokers without other objective assessments consistent with COPD. Hence, our objective was to develop a machine-learning and CT texture-analysis pipeline to dichotomize ex-smokers with normal and abnormal DL CO (DL CO ≥ 75% pred and DL CO <75% pred). In this retrospective study, 71 ex-smokers (50–85 yrs) without COPD underwent spirometry, plethysmography, thoracic CT, and 3He MRI to generate ventilation defect percent (VDP) and apparent diffusion coefficients (ADC). PyRadiomics was utilized to extract 496 CT texture-features; Boruta and principal component analysis were used for feature selection and various models were investigated for classification. Machine-learning classifiers were evaluated using area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and F1-measure. Of 71 ex-smokers without COPD, 29 with mildly abnormal DL CO had significantly different MRI ADC (p <.001), residual-volume to total-lung-capacity ratio (p =.003), St. George's Respiratory Questionnaire (p =.029), and six-minute-walk distance (6MWD) (p <.001), but similar relative area of the lung < −950 Hounsfield-units (RA 950) (p =.9) compared to 42 ex-smokers with normal DL CO. Logistic-regression machine-learning mixed-model trained on selected texture-features achieved the best classification accuracy of 87%. All clinical and imaging measurements were outperformed by high-high-pass filter high-gray-level-run-emphasis texture-feature (AUC = 0.81), which correlated with DL CO (ρ = −0.29, p =.02), MRI ADC (ρ = 0.23, p =.048), and 6MWD (ρ = −0.25, p =.02). In ex-smokers with no CT evidence of emphysema, machine-learning models exclusively trained on CT texture-features accurately classified ex-smokers with abnormal diffusing capacity, outperforming conventional quantitative CT measurements. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: 129Xe MRI has been developed to noninvasively visualize and quantify the functional consequence of airway obstruction in asthma. Its widespread application requires evidence of intersite reproducibility and agreement. Our objective was to evaluate reproducibility and agreement of 129Xe ventilation MRI measurements in severe asthmatics at two sites.Materials and Methods: In seven adults with severe asthma, 129Xe ventilation MRI was acquired pre- and post-bronchodilator at two geographic sites within 24-hours. 129Xe MRI signal-to-noise ratio (SNR) was calculated and ventilation abnormalities were quantified as the whole-lung and slice-by-slice ventilation defect percent (VDP). Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to determine intersite 129Xe VDP reproducibility and agreement.Results: Whole-lung and slice-by-slice 129Xe VDP measured at both sites were correlated and reproducible (pre-bronchodilator: whole-lung ICC = 0.90, p = 0.005, slice-by-slice ICC = 0.78, p < 0.0001; post-bronchodilator: whole-lung ICC = 0.94, p < 0.0001, slice-by-slice ICC = 0.83, p < 0.0001) notwithstanding intersite differences in the 129Xe-dose-equivalent-volume (101 ± 15 mL site 1, 49 ± 6 mL site 2, p < 0.0001), gas-mixture (129Xe/4He site 1; 129Xe/N2 site 2) and SNR (40 ± 19 site 1, 23 ± 5 site 2, p = 0.02). Qualitative 129Xe gas distribution differences were observed between sites and slice-by-slice 129Xe VDP, but not whole-lung 129Xe VDP, was significantly lower at site 1 (pre-bronchodilator VDP: whole-lung bias = -3%, p > 0.99, slice-by-slice bias = -3%, p = 0.0001; post-bronchodilator VDP: whole-lung bias = -2%, p = 0.59, slice-by-slice-bias = -2%, p = 0.0003).Conclusion: 129Xe MRI VDP at two different sites measured within 24-hours in the same severe asthmatics were correlated. Qualitative and quantitative intersite differences in 129Xe regional gas distribution and VDP point to site-specific variability that may be due to differences in gas-mixture composition or SNR. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The relationships between computed tomography (CT) pulmonary vascularity and MRI ventilation is not well-understood in chronic obstructive pulmonary disease (COPD) patients. Our objective was to evaluate CT pulmonary vascular and MRI ventilation measurements in ex-smokers and to investigate their associations and how such measurements change over time.Materials and Methods: Ninety ex-smokers (n = 41 without COPD 71 ± 10 years and n = 49 COPD 71 ± 8 years) provided written informed-consent to an ethics-board approved protocol and underwent imaging and pulmonary-function-tests twice, 31 ± 7 months apart. 3He MRI was acquired to generate ventilation-defect-percent (VDP). CT measurements of the relative area-of-the-lung with attenuation <-950 Hounsfield units (RA950), pulmonary vascular total-blood-volume (TBV) and percent of vessels with radius < one voxel (PV1) were evaluated.Results: At baseline, there were significant differences in RA950 (p = 0.0001), VDP (p = 0.0001), total-blood-volume (p = 0.0001) and PV1 (p = 0.01) between ex-smokers and COPD participants as well as for VDP (p = 0.0001) in COPD participants with and without emphysema. The annual FEV1 change (-40 ± 93 mL/year) was not different among participant subgroups (p = 0.87), but the annual RA950 (p = 0.01) and PV1 (p = 0.007) changes were significantly different in participants with an accelerated annual FEV1 decline as compared to participants with a diminished annual FEV1 decline. There were significant but weak relationships for PV1 with FEV1%pred (p = 0.02), FEV1/FVC (p = 0.001), and log RA950 (p = 0.0001), but not VDP (p=0.20). The mean change in PV1 was also weakly but significantly related to the change in RA950 (p = 0.02).Conclusion: CT pulmonary vascular measurements were significantly different in ex-smokers and participants with COPD and related to RA950 but not VDP worsening over 2.5 years. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: In patients with severe emphysema and poor quality of life, bronchoscopic lung volume reduction (BLVR) may be considered and guided based on lobar emphysema severity. In particular, x-ray computed tomography (CT) emphysema measurements are used to identify the most diseased and the second-most diseased lobes as BLVR targets. Inhaled gas magnetic resonance imaging (MRI) also provides chronic obstructive pulmonary disease (COPD) biomarkers of lobar emphysema and ventilation abnormalities. Our objective was to retrospectively evaluate CT and MRI biomarkers of lobar emphysema and ventilation in patients with COPD eligible for BLVR. We hypothesized that MRI would provide complementary biomarkers of emphysema and ventilation that help determine the most appropriate lung lobar targets for BLVR in patients with COPD.Materials and Methods: We retrospectively evaluated 22 BLVR-eligible patients from the Thoracic Imaging Network of Canada cohort (diffusing capacity of the lung for carbon monoxide = 37 ± 12%predicted, forced expiratory volume in 1 second = 34 ± 7%predicted, total lung capacity = 131 ± 17%predicted, and residual volume = 216 ± 36%predicted). Lobar CT emphysema, measured using a relative area of <-950 Hounsfield units (RA950) and MRI ventilation defect percent, was independently used to rank lung lobe disease severity.Results: In 7 of 22 patients, there were different CT and MRI predictions of the most diseased lobe. In some patients, there were large ventilation defects in lobes not targeted by CT, indicative of a poorly ventilated lung. CT and MRI classification of the most diseased and the second-most diseased lobes showed a fair-to-moderate intermethod reliability (Cohen κ = 0.40-0.59).Conclusions: In this proof-of-concept retrospective analysis, quantitative MRI ventilation and CT emphysema measurements provided different BLVR targets in over 30% of the patients. The presence of large MRI ventilation defects in lobes next to CT-targeted lobes might also change the decision to proceed or to guide BLVR to a different lobar target. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: 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.Materials and Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Ventilation heterogeneity is a hallmark feature of asthma. Our objective was to evaluate ventilation heterogeneity in patients with severe asthma, both pre- and post-salbutamol, as well as post-methacholine (MCh) challenge using the lung clearance index, free-breathing pulmonary 1H magnetic resonance imaging (FDMRI), and inhaled-gas MRI ventilation defect percent (VDP).Materials and Methods: Sixteen severe asthmatics (49 ± 10 years) provided written informed consent to an ethics board-approved protocol. Spirometry, plethysmography, and multiple breath nitrogen washout to measure the lung clearance index were performed during a single visit within 15 minutes of MRI. Inhaled-gas MRI and FDMRI were performed pre- and post-bronchodilator to generate VDP. For asthmatics with forced expiratory volume in 1 second (FEV1) >70%predicted, MRI was also performed before and after MCh challenge. Wilcoxon signed-rank tests, Spearman correlations, and a repeated-measures analysis of variance were performed.Results: Hyperpolarized 3He (P = .02) and FDMRI (P = .02) VDP significantly improved post-salbutamol and for four asthmatics who could perform MCh (n = 4). 3He and FDMRI VDP significantly increased at the provocative concentration of MCh, resulting in a 20% decrease in FEV1 (PC20) and decreased post-bronchodilator (P = .02), with a significant difference between methods (P = .01). FDMRI VDP was moderately correlated with 3He VDP (ρ = .61, P = .01), but underestimated VDP relative to 3He VDP (-6 ± 9%). Whereas 3He MRI VDP was significantly correlated with the lung clearance index, FDMRI was not (ρ = .49, P = .06).Conclusions: FDMRI VDP generated in free-breathing asthmatic patients was correlated with static inspiratory breath-hold 3He MRI VDP but underestimated VDP relative to 3He MRI VDP. Although less sensitive to salbutamol and MCh, FDMRI VDP may be considered for asthma patient evaluations at centers without inhaled-gas MRI. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Evidence-based treatment and management for patients with bronchiectasis remain challenging. There is a need for regional disease measurements as focal distribution of disease is common. Our objective was to evaluate the ability of magnetic resonance imaging (MRI) to detect regional ventilation impairment and response to airway clearance therapy (ACT) in patients with noncystic fibrosis (CF) bronchiectasis, providing a new way to objectively and regionally evaluate response to therapy.Materials and Methods: Fifteen participants with non-CF bronchiectasis and 15 age-matched healthy volunteers provided written informed consent to an ethics board-approved Health Insurance Portability and Accountability Act-compliant protocol and underwent spirometry, plethysmography, computed tomography (CT), and hyperpolarized 3He MRI. Bronchiectasis patients also completed a Six-Minute Walk Test, the St. George's Respiratory questionnaire, and Patient Evaluation Questionnaire (PEQ), and returned for a follow-up visit after 3 weeks of daily oscillatory positive expiratory pressure use. CT evidence of bronchiectasis was qualitatively reported by lobe, and MRI ventilation defect percent (VDP) was measured for the entire lung and individual lobes.Results: CT evidence of bronchiectasis and abnormal VDP (14 ± 7%) was observed for all bronchiectasis patients and no healthy volunteers. There was CT evidence of bronchiectasis in all lobes for 3 patients and in 3 ± 1 lobes (range = 1-4) for 12 patients. VDP in lobes with CT evidence of bronchiectasis (19 ± 12%) was significantly higher than in lobes without CT evidence of bronchiectasis (8 ± 5%, P = .001). For patients, VDP in lung lobes with (P < .0001) and without CT evidence of bronchiectasis (P = .006) was higher than in healthy volunteers (3 ± 1%). For all patients, mean PEQ-ease-bringing-up-sputum (P = .048) and PEQ-patient-global-assessment (P = .01) were significantly improved post-oscillatory positive expiratory pressure. An improvement in regional VDP greater than the minimum clinical important difference was observed for 8 of the 14 patients evaluated.Conclusions: There was CT and MRI evidence of structure-function abnormalities in patients with bronchiectasis; in approximately half, there was evidence of ventilation improvements after airway clearance therapy. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Pulmonary functional magnetic resonance imaging provides a way to quantify ventilation and its heterogeneity-a hallmark finding in chronic obstructive pulmonary disease (COPD). Unfortunately, the etiology and physiological meaning of ventilation defects and their relationship to pulmonary function and symptoms in COPD are not well understood. Another biomarker of ventilation heterogeneity is provided by the "poorly communicating fraction" (PCF), and is calculated as the ratio of total lung capacity to alveolar volume made using whole-body plethysmography. Our objective was to compare ventilation heterogeneity using hyperpolarized (3)He magnetic resonance imaging (MRI) and PCF measurements in elderly never-smokers and in ex-smokers with COPD.Materials and Methods: One hundred forty-six participants (71 ± 8 years, range = 48-87 years) provided written informed consent including 45 elderly never-smokers (71 ± 6 years, range = 61-84 years) and 101 ex-smokers with COPD (71 ± 8 years, range = 48-87 years). During a single 2-hour visit, spirometry, plethysmography, and hyperpolarized (3)He MRI were acquired. The MRI-derived ventilation defect percent (VDP) and plethysmography measurements were acquired and PCF values were calculated. Linear regression, Pearson correlations, and Bland-Altman analysis were used to evaluate the relationships for PCF and MRI VDP.Results: PCF (P < 0.001) and VDP (P < 0.001) were significantly increased with increasing COPD severity. There was a significant relationship for VDP and PCF (r = 0.68, P < 0.001) in all subjects and COPD subjects alone (r = 0.61, P < 0.001). Bland-Altman analysis showed that PCF and VDP were significantly different (mean bias = 9.7, upper limit = 32, lower limit = -13, P < 0.001), and in severe-grade COPD, PCF overestimates of VDP were significantly greater.Conclusions: In elderly never-smokers and in ex-smokers with COPD, PCF and VDP are moderately correlated estimates of COPD ventilation heterogeneity that may be reflecting similar pathophysiology. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: (3)He magnetic resonance imaging (MRI) can be used to quantify functional responses to asthma therapy and provocation. Ventilation imaging offers quantitative information beyond ventilation defects that have not yet been exploited. Therefore, our objective was to evaluate hyperpolarized (3)He MRI ventilation defect percent (VDP) and compare this and pulmonary function measurements to ventilation image texture features and their changes post-bronchodilator administration in patients with asthma. Materials and Methods: Volunteers with a diagnosis of asthma provided written informed consent to an ethics board-approved protocol and underwent pulmonary function tests and MRI before and after salbutamol inhalation. MR images were analyzed using VDP, and their texture was evaluated via gray-level run-length matrices. These texture classifiers were compared to VDP in responders to bronchodilation based on VDP (VDP responders) and forced expiratory volume in 1 s (FEV1) (FEV1 responders). Results: In total, 47 patients with asthma (18 males 39 ± 13 years, FEV1 = 79 ± 21%) reported significantly improved FEV1, FEV1/forced vital capacity (FVC), residual volume (RV)/total lung capacity (TLC) (all P = .0001) and VDP (P = .01) post-salbutamol. Post-salbutamol, VDP responders and nonresponders to salbutamol were significantly different for coarse-texture features including long-run emphasis (LRE) and long-run, low gray-level emphasis (LRLGE, both P < .05) and for FEV1 responders to salbutamol, there was significantly different long-run, high gray-level emphasis (LRHGE, P = .04). There were significant relationships for VDP with LRE (R = .50, P = .0003), LRLGE (R = .34, P = .02), and LRHGE (R = .56, P = .0001). Receiver operating characteristic curves showed VDP with the strongest performance (AUC = .92), followed by coarse-texture classifier LRHGE (AUC = .83), FEV1 (AUC = .80), LRE (AUC = .66), FVC (AUC = .58), and LRLGE (AUC = .42). Conclusions: In patients with asthma, differences in ventilation patchiness post-salbutamol can be quantified using coarse-texture classifiers that are significantly different in bronchodilator responders. [ABSTRACT FROM AUTHOR]

Rationale and Objectives Hyperpolarized 3 He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP). Materials and Methods Sixty ex-smokers without airflow limitation provided written informed consent to 3 He MRI, computed tomography (CT), and pulmonary function tests in a single visit. 3 He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤−950 HU, RA 950 ) and airway morphology (wall area percent [WA%], lumen area [LA] and LA normalized to body surface area [LA/BSA]). Results In 42 ex-smokers, there was abnormally elevated VDP and no significant differences for pulmonary function, RA 950 , or airway measurements compared to 18 ex-smokers with normal VDP. Ex-smokers with abnormally elevated VDP reported significantly greater 3 He ADC in the apical lung (right upper lobe [RUL], P = .02; right middle lobe [RML], P = .04; and left upper lobe [LUL], P = .009). Whole lung (r = 0.40, P = .001) and lobar VDP (RUL, r = 0.32, P = .01; RML, r = 0.46, P = .002; right lower lobe [RLL], r = 0.38, P = .003; LUL, r = 0.35, P = .006; and left lower lobe, r = 0.37, P = .004) correlated with regional 3 He ADC. Although whole-lung VDP and CT airway morphology measurements were not correlated, regional VDP was correlated with RUL LA (r = −0.37, P = .004), LA/BSA (r = −0.42, P = .0008), RLL WA% (r = 0.28, P = .03), LA (r = −0.28, P = .03), and LA/BSA (r = −0.37, P = .004). Conclusions Abnormally elevated VDP in ex-smokers without airflow limitation was coincident with very mild emphysema detected using MRI and regional airway remodeling detected using CT representing a subclinical obstructive lung disease phenotype. [ABSTRACT FROM AUTHOR]

Rationale and Objectives In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing 1 H magnetic resonance imaging (FDMRI) to hyperpolarized 3 He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. Materials and Methods All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and 3 He MRI, and these were compared using analysis of variance and Pearson correlations. Results Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and 3 He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively ( P < .001; bias = −16 ± 9%). In COPD subjects, FDMRI was significantly correlated with 3 He MRI VDP (r = .88; P = .0001), 3 He MRI apparent diffusion coefficient (r = .71; P < .05), airways resistance (r = .60; P < .05), and RA 950 (r = .80; P < .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and 3 He MRI VDP (18 ± 9%) were significantly different ( P < .001) and not correlated ( P > .05). The Dice similarity coefficient (DSC) for FDMRI and 3 He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects ( P > .05); the DSC for FDMRI ventilation defects and CT RA 950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects ( P < .01). Conclusions FDMRI and 3 He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with 3 He ventilation defects and emphysema. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Hyperpolarized ³He magnetic resonance imaging (MRI) previously revealed the temporal and spatial hetero-geneity of ventilation defects in asthmatics, but these findings have not been used in treatment studies or to guide personalized therapy. Our objective was to exploit the temporal and spatial information inherent to ³He MRI and develop image processing methods to generate pulmonary ventilation temporal-spatial maps that could be used to measure, optimize, and guide asthma therapy. Materials and Methods: In this proof-of-concept study, seven asthmatics provided written informed consent to an approved protocol and underwent spirometry and ³He MRI on three occasions, each 5 ± 2 days apart. A registration and segmentation pipeline was developed to generate three-dimensional, temporal-spatial, pulmonary function maps. Briefly, ³He ventilation images were segmented to generate ventilation masks that were coregisfered and voxels classified according to their temporal behavior. This enabled the regional mapping of temporally persistent and intermittent ventilation defects that were normalized to the ¹H MRI thoracic cavity volume to generate persis-tent ventilation defect percent (VDPP) and intermittent ventilation defect percent (VDP|). Results: ³He temporal-spatial pulmonary function maps identified temporally persistent and intermittent ventilation defects. VDP| was significantly greater in the posterior (P = .04) and inferior (P = .04) lung as compared to the anterior and superior lung. Persistent and inter-mittent ventilation defect percent were strongly correlated with forced expiratory volume in one second/forced vital capacity (VDPP: r = -0.87, P = .01 ; VDP,: r = -0.96, P = .0008). Conclusions: Temporal-spatial pulmonary maps generated from ³He MRI can be used to quantify temporally persistent and intermittent ventilation defects as asthma intermediate end points and targets for therapy. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: High-resolution computed tomography (CT) measurements of emphysema typically use Hounsfield unit (HU) density histogram thresholds or observer scores based on regions of low x-ray attenuation. Our objective was to develop an automated measurement of emphysema using principal component analysis (PCA) of the CT density histogram. Materials and Methods: Ninety-seven ex-smokers, including 53 subjects with chronic obstructive pulmonary disease (COPD) and 44 asymptomatic subjects (AEs), provided written informed consent to imaging as well as plethysmography and spirometry. We applied PCA to the CT density histogram to generate whole lung and regional density histogram principal components including the first and second components and the sum of both principal components (density histogram principal component score [DHPCS]). Significant relationships for DHPCS with single HU thresholds, pulmonary function measurements, an expert''s emphysema score, and hyperpolarized 3He magnetic resonance imaging apparent diffusion coefficients (ADCs) were determined using linear regression and Pearson coefficients. Receiver operator characteristics analysis was performed using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) as the independent diagnostic. Results: There was a significant difference (P < .0001) between AE and COPD subjects for DHPCS; FEV1/FVC; diffusing capacity of lung for carbon monoxide%predicted; attenuation values below −950, −910, and −856 HU; and 3He ADCs. There were significant correlations for DHPCS with FEV1/FVC (r = −0.85, P < .0001); diffusing capacity of lung for carbon monoxide%predicted (r = −0.67, P < .0001); attenuation values below −950/−910/−856 HU (r = 0.93/0.96/0.76, P < .0001); and 3He ADCs (r = 0.85, P < .0001). Receiver operator characteristics analysis showed a 91% classification rate for DHPCS. Conclusions: We generated an automated emphysema score using PCA of the CT density histogram with a 91% COPD classification rate that showed strong and significant correlations with pulmonary function tests, single HU thresholds, and 3He magnetic resonance imaging ADCs. [Copyright &y& Elsevier]

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 (3He) MRI. Therefore the objective of this study was to compare the reproducibility and spatial agreement of manual and semiautomated segmentation of 3He 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 3He 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 1H MRI thoracic cavity for coregistration to the 3He cluster-map, generating VDV and VV. Results: We compared manual segmentation performed by an expert observer and semiautomated measurements of 3He 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 3He MRI provides excellent inter- and intraobserver precision with high spatial and quantitative agreement with manual measurements enabling its use in longitudinal studies. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Lung resection for primary bronchogenic carcinoma in the setting of chronic obstructive pulmonary disease often requires a detailed assessment of lung function to avoid perioperative complications and long-term disability. The aim of this study was to test the hypothesis that a novel technique of spiral computed tomographic (CT) subtraction imaging provides accuracy equal to the current standard of radioisotope perfusion scintigraphy in predicting postoperative lung function. Methods and Materials: Preoperative lung function, radioisotope perfusion scintigraphy, spiral CT subtraction imaging, and assessment of postoperative lung function were performed in 25 patients with surgically resectable primary bronchogenic carcinoma. Comparisons of predicted postoperative lung function between the two modalities and to true postoperative lung function were performed using Pearson's correlation and linear regression analysis. Results: Among the 25 patients enrolled in the study, there was a high degree of agreement between the predicted value of postoperative forced expiratory lung volume in 1 second (FEV(1)) generated on novel contrast CT subtraction imaging and that on radioisotope perfusion scintigraphy (r = 0.96, P < .001). Furthermore, there was a strong correlation between the predicted and actual postoperative FEV(1) values for both imaging modalities (r = 0.87, P < .001, and r = 0.88, P < .001, respectively), among the 14 patients completing the study protocol. Conclusion: A novel technique of CT subtraction imaging is equally accurate at predicting postoperative lung function as radioisotope perfusion scintigraphy, which may obviate the need for additional nuclear imaging in the context of the preoperative assessment of resectable lung cancer in high-risk patients. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Lung resection for primary bronchogenic carcinoma in the setting of chronic obstructive pulmonary disease often requires a detailed assessment of lung function to avoid perioperative complications and long-term disability. The aim of this study was to test the hypothesis that a novel technique of spiral computed tomographic (CT) subtraction imaging provides accuracy equal to the current standard of radioisotope perfusion scintigraphy in predicting postoperative lung function. Methods and Materials: Preoperative lung function, radioisotope perfusion scintigraphy, spiral CT subtraction imaging, and assessment of postoperative lung function were performed in 25 patients with surgically resectable primary bronchogenic carcinoma. Comparisons of predicted postoperative lung function between the two modalities and to true postoperative lung function were performed using Pearson''s correlation and linear regression analysis. Results: Among the 25 patients enrolled in the study, there was a high degree of agreement between the predicted value of postoperative forced expiratory lung volume in 1 second (FEV1) generated on novel contrast CT subtraction imaging and that on radioisotope perfusion scintigraphy (r = 0.96, P < .001). Furthermore, there was a strong correlation between the predicted and actual postoperative FEV1 values for both imaging modalities (r = 0.87, P < .001, and r = 0.88, P < .001, respectively), among the 14 patients completing the study protocol. Conclusion: A novel technique of CT subtraction imaging is equally accurate at predicting postoperative lung function as radioisotope perfusion scintigraphy, which may obviate the need for additional nuclear imaging in the context of the preoperative assessment of resectable lung cancer in high-risk patients. [Copyright &y& Elsevier]

Rationale and Objectives: We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using 3He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the 3He apparent diffusion coefficient (ADC) and center coronal slice 3He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons. Materials and Methods: Twenty-four subjects who provided written informed consent (15 males; mean age 67 ±7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 ± 2 minutes (same-day rescan) and again 7 ± 2 days later (7-day rescan). 3He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin''s concordance correlation coefficients (CCC). Results: ADC reproducibility was high for same-day rescan (r2 = 0.934) and 7-day rescan (r2 = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r2 = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r2 = 0.576, P < .001, ICC 0.74, CCC 0.75, P < .01). Conclusions: Hyperpolarized 3He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV. [Copyright &y& Elsevier]

Rationale and Objectives: Hyperpolarized 3He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified 3He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders. Materials and Methods: Hyperpolarized 3He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67 ± 6 years) scanned twice within 7 ± 2 minutes and again 7 ± 2 days later. A younger cohort of 24 subjects (mean 44 ± 10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices. Results: Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63–74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52 ± 34 cm3), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53 ± 35 cm3) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48 ± 39 cm3). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10–12%. Conclusion: Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from 3He studies of elderly subjects. [Copyright &y& Elsevier]

Abstract: 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 3.0T. 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. [Copyright &y& Elsevier]