Imaging how and where we breathe oxygen: Another Big Short?

The Big Short tells the story of a small group of skeptics who profited from the financial crisis in 2007 by betting against collateralized (mortgage) debt obligations (CDO). Importantly, the novel paints a clear picture of the eccentric nature of contrarians who think divergently and against the grain or bet against an accepted truth or “sure” thing. In a similar manner, Ishii and co-workers’ recent work describes their team’s development of a pulmonary imaging technology that provides divergent and disruptive in vivo lung measurements of oxygen partial pressure in the context of the prevailing and longstanding consensus around FEV1 as the definitive diagnostic of chronic lung disease. The Big Short tells the story of a small group of skeptics who profited from the financial crisis in 2007 by betting against collateralized (mortgage) debt obligations (CDO). Importantly, the novel paints a clear picture of the eccentric nature of contrarians who think divergently and against the grain or bet against an accepted truth or “sure” thing. In a similar manner, Ishii and co-workers’ recent work describes their team’s development of a pulmonary imaging technology that provides divergent and disruptive in vivo lung measurements of oxygen partial pressure in the context of the prevailing and longstanding consensus around FEV1 as the definitive diagnostic of chronic lung disease

Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer.

OBJECTIVE: In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients. MATERIALS AND METHODS: Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram RESULTS: Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = .02) and FEV1/FVC (p = .04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA950, p \u3c .001). There were significant relationships for whole-lung VDP (p \u3c .05), but not RECIST or tumour-lobe VDP measurements with pulmonary function and exercise measurements. Preliminary analysis for non-tumour burden ventilation abnormalities using Reader-operator-characteristic (ROC) curves reflected a 94% classification rate for smoking pack-years, 93% for FEV1/FVC and 82% for RA950. ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV1/FVC (0.92/0.80/4.6/0.3), RA950 (0.92/0.80/4.6/0.3) and RECIST (0.58/0.80/2.9/1.1). CONCLUSIONS: In this prospectively planned interim-analysis of a larger clinical trial, NSCLC patients were classified based on COPD imaging phenotypes. A proof-of-concept evaluation showed that FEV1/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy

Chronic Obstructive Pulmonary Disease: Thoracic CT Texture Analysis and Machine Learning to Predict Pulmonary Ventilation

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study

Pulmonary Imaging Biomarkers of Gas Trapping and Emphysema in COPD: (3)He MR Imaging and CT Parametric Response Maps

PURPOSE: To directly compare magnetic resonance (MR) imaging and computed tomography (CT) parametric response map (PRM) measurements of gas trapping and emphysema in ex-smokers both with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Participants provided written informed consent to a protocol that was approved by a local research ethics board and Health Canada and was compliant with the HIPAA (Institutional Review Board Reg. #00000940). The prospectively planned study was performed from March 2014 to December 2014 and included 58 ex-smokers (mean age, 73 years ± 9) with (n = 32; mean age, 74 years ± 7) and without (n = 26; mean age, 70 years ± 11) COPD. MR imaging (at functional residual capacity plus 1 L), CT (at full inspiration and expiration), and spirometry or plethysmography were performed during a 2-hour visit to generate ventilation defect percent (VDP), apparent diffusion coefficient (ADC), and PRM gas trapping and emphysema measurements. The relationships between pulmonary function and imaging measurements were determined with analysis of variance (ANOVA), Holm-Bonferroni corrected Pearson correlations, multivariate regression modeling, and the spatial overlap coefficient (SOC). RESULTS: VDP, ADC, and PRM gas trapping and emphysema (ANOVA, P \u3c .001) measurements were significantly different in healthy ex-smokers than they were in ex-smokers with COPD. In all ex-smokers, VDP was correlated with PRM gas trapping (r = 0.58, P \u3c .001) and with PRM emphysema (r = 0.68, P \u3c .001). VDP was also significantly correlated with PRM in ex-smokers with COPD (gas trapping: r = 0.47 and P = .03; emphysema: r = 0.62 and P \u3c .001) but not in healthy ex-smokers. In a multivariate model that predicted PRM gas trapping, the forced expiratory volume in 1 second normalized to the forced vital capacity (standardized coefficients [βS] = -0.69, P = .001) and airway wall area percent (βS = -0.22, P = .02) were significant predictors. PRM emphysema was predicted by the diffusing capacity for carbon monoxide (βS = -0.29, P = .03) and VDP (βS = 0.41, P = .001). Helium 3 ADC values were significantly elevated in PRM gas-trapping regions (P \u3c .001). The spatial relationship for ventilation defects was significantly greater with PRM gas trapping than with PRM emphysema in patients with mild (for gas trapping, SOC = 36% ± 28; for emphysema, SOC = 1% ± 2; P = .001) and moderate (for gas trapping, SOC = 34% ± 28; for emphysema, SOC = 7% ± 15; P = .006) COPD. For severe COPD, the spatial relationship for ventilation defects with PRM emphysema (SOC = 64% ± 30) was significantly greater than that for PRM gas trapping (SOC = 36% ± 18; P = .01). CONCLUSION: In all ex-smokers, ADC values were significantly elevated in regions of PRM gas trapping, and VDP was quantitatively and spatially related to both PRM gas trapping and PRM emphysema. In patients with mild to moderate COPD, VDP was related to PRM gas trapping, whereas in patients with severe COPD, VDP correlated with both PRM gas trapping and PRM emphysema

Pulmonary Imaging Phenotypes of Chronic Obstructive Pulmonary Disease Using Multiparametric Response Maps

Background Pulmonary imaging of chronic obstructive pulmonary disease (COPD) has focused on CT or MRI measurements, but these have not been evaluated in combination. Purpose To generate multiparametric response map (mPRM) measurements in ex-smokers with or without COPD by using volume-matched CT and hyperpolarized helium 3

Free-breathing Pulmonary (1)H and Hyperpolarized (3)He MRI: Comparison in COPD and Bronchiectasis.

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 \u3c .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 \u3c .05), airways resistance (r = .60; P \u3c .05), and RA950 (r = .80; P \u3c .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P \u3c .001) and not correlated (P \u3e .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 \u3e .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P \u3c .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

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 \u3c .0001; ventilation percentage: 99% [IQR: 1%] vs 94% [IQR: 5%], P \u3c .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 \u3c .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 \u3c .0001), ratio of residual volume to total lung capacity (ρ = -0.68, P \u3c .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 \u3c .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

Through the Looking Glass and What Was Found There: Imaging Biomarkers of Chronic Obstructive Pulmonary Disease

Through the Looking-Glass and What Alice Found There (1) describes adventures in a new and alternative world that Alice discovered after stepping through to the other side of a mirror. Importantly, one of this enduring novel’s underlying themes is the presence of inverse reflections and the notion that in the looking-glass world, one’s basic assumptions can be reversed. In a similar manner, in this issue of the Journal, Bodduluri and colleagues (pp. 1404–1410) present a new “through the looking-glass” way of evaluating normal lung regions that, surprisingly, reveals gas trapping not detected using the typical X-ray computed tomography (CT) density thresholds (2). Like the looking-glass adventures, this approach is intuitive and stimulating, and these findings are both clinically relevant and revelatory. Notably, their findings add to the substantial body of work that stems from the Genetic Epidemiology of COPD (COPDGene) study (3), which has improved our understanding of chronic obstructive pulmonary disease (COPD) and provided novel biomarkers of COPD using high-resolution CT. Although COPDGene was designed to identify genetic factors associated with COPD, reports of CT imaging biomarkers as objective measures of disease have dominated, in that nearly half of all COPDGene publications describe CT findings (using PubMed “COPDGene” and “COPDGene and CT”)

A framework for Fourier-decomposition free-breathing pulmonary 1H MRI ventilation measurements

PURPOSE: To develop a rapid Fourier decomposition (FD) free-breathing pulmonary METHODS: We acquired MRI in 20 asthmatic subjects using a balanced steady-state free precession (bSSFP) sequence optimized for ventilation imaging. 2D RESULTS: For lung segmentation, there was a DSC of 95 ± 1.5% and MAD of 2.3 ± 0.5 mm, and for registration there was a DSC of 97 ± 0.8%, MAD of 1.6 ± 0.4 mm and TRE of 3.6 ± 1.2 mm. Reproducibility for segmentation DSC (CoV/ICC = 0.5%/0.92), registration TRE (CoV/ICC = 0.4%/0.98), and FD-VDP (Cov/ICC = 3.9%/0.97) was high. The pipeline required 10 min/subject. FD-VDP was correlated with CONCLUSIONS: We developed and evaluated a pipeline that provides a rapid and precise method for FDMRI ventilation maps