Damien Pike

Hyperpolarized (3)he ventilation defects used to predict pulmonary exacerbations in mild to moderate chronic obstructive pulmonary disease.

PURPOSE To evaluate the predictive value of imaging and clinical and physiological measurements of chronic obstructive pulmonary disease ( COPD chronic obstructive pulmonary disease ) in patients monitored for more than 5 years for pulmonary exacerbations that required hospitalization. MATERIALS AND METHODS Exacerbations requiring hospitalization were monitored over 5 years in 91 subjects who provided written informed consent. Study was local research ethics board and Health Canada approved and HIPAA compliant. Subjects with COPD chronic obstructive pulmonary disease underwent spirometry, plethysmography, diffusing capacity of carbon monoxide, St Georges Respiratory Questionnaire, 6-minute walk test, and imaging. Computed tomographic (CT) wall area and relative area with attenuation values less than -950 HU ( RA950 relative area with attenuation values less than -950 HU ), helium 3 ((3)He) magnetic resonance (MR) imaging ventilation defect percentage ( VDP ventilation defect percentage ), and apparent diffusion coefficient were generated. Zero-inflated Poisson model was used to compare number of hospitalizations with lung function and imaging measurements. RESULTS Twenty-four subjects were hospitalized 58 times and had significantly worse forced expiratory volume in 1 second ( FEV1 forced expiratory volume in 1 second ) (P < .0001), CT RA950 relative area with attenuation values less than -950 HU (P = .02), and (3)He VDP ventilation defect percentage (P < .0001) than values in 67 subjects who were not hospitalized. In mild to moderate COPD chronic obstructive pulmonary disease , nine hospitalized subjects had significantly worse FEV1 forced expiratory volume in 1 second (P = .02) and (3)He VDP ventilation defect percentage (P = .02) than values in 52 subjects who were not hospitalized. (3)He VDP ventilation defect percentage was quantitatively related to CT airway morphology (r = 0.26, P = .01) and quantitatively (r = 0.61, P < .0001) and spatially related to emphysema; this spatial relationship was significantly greater for hospitalized patients with COPD chronic obstructive pulmonary disease than unhospitalized patients (P = .0006). For all subjects, number of prior hospitalizations (P < .0001), 6-minute walk test distance (P < .0001), CT RA950 relative area with attenuation values less than -950 HU (P = .03), and (3)He VDP ventilation defect percentage (P = .002) were significantly related to number of hospitalizations. For 61 subjects with mild to moderate COPD chronic obstructive pulmonary disease , only (3)He VDP ventilation defect percentage was significantly associated with COPD chronic obstructive pulmonary disease exacerbations (P = .01). CONCLUSION (3)He MR imaging VDP ventilation defect percentage represents a mixed airways-emphysema phenotype and helps identify subjects with mild to moderate COPD chronic obstructive pulmonary disease who are at risk for exacerbation that requires hospitalization.

Ultra-short echo-time pulmonary MRI: evaluation and reproducibility in COPD subjects with and without bronchiectasis.

To evaluate ultra‐short‐echo‐time (UTE) MRI pulmonary signal‐intensity measurements and reproducibility in chronic obstructive pulmonary disease (COPD).

COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity?

PURPOSE To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease. MATERIALS AND METHODS Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St Georges Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements. RESULTS Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01). CONCLUSION In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms.

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 < .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 < .001) and with PRM emphysema (r = 0.68, P < .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 < .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 < .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.

Longitudinal Computed Tomography and Magnetic Resonance Imaging of COPD: Thoracic Imaging Network of Canada (TINCan) Study Objectives

Although the human and societal burden and cost of COPD is staggering, there are few clinical tools that provide earlier diagnoses or a means to regionally monitor disease in a way that might lead to improved therapies and outcomes. In acknowledgement of the current gaps in COPD therapy, the objective of the Thoracic Imaging Network of Canada (TINCan) is to improve COPD patient phenotyping through imaging, to provide methods and imaging-based intermediate endpoints for the development of new treatments, and to evaluate disease progression and patient-based outcomes in COPD patients and those at risk of COPD. Here we summarize and outline the TINCan study protocol and describe our objectives. TINCan is a prospective study that aims to identify and quantify novel COPD phenotypes from thoracic computed tomography (CT) and thoracic hyperpolarized noble gas magnetic resonance imaging (MRI) in 200 ex-smokers, 50 years of age or greater, including asymptomatic ex-smokers with normal pulmonary function and Global initiative for chronic Obstructive Lung Disease (GOLD) Unclassified (U) , and GOLD stages I-IV patients. Baseline and 2-year follow-up measurements will be acquired using spirometry, plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), St. Georges Respiratory Questionnaire (SGRQ), 6-minute walk test (6MWT), thoracic CT and hyperpolarized helium-3 (3He) and xenon 129 (129Xe) MRI. TINCan provides a unique opportunity to quantify and compare novel lung structure-function measurements and investigate their relationship with well-established clinical measurements and outcomes. Such intermediate endpoints of COPD may be used to stratify patients for personalized treatments and to develop new treatments to improve outcomes, a long-standing clinical goal.

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

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

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

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

One, two and three-dimensional ultrasound measurements of carotid atherosclerosis before and after cardiac rehabilitation: preliminary results of a randomized controlled trial

BackgroundIt is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.MethodsCarotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed consent to participate in this randomized controlled trial. We maintained blinding for this ongoing study by representing treatment and control groups as A or B, although we did not identify which of A or B was treatment or control. Carotid IMT, TPA, TPV and VWV were measured before and after CCR as were changes in body mass index (BMI), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP).ResultsThere were no significant differences in US measurements or risk factors between groups A and B. There was no significant change in carotid ultrasound measurements for group A (IMT, p = .728; TPA, p = .629; TPV, p = .674; VWV, p = .507) or B (IMT, p = .054; TPA, p = .567; TPV, p = .773; VWV, p = .431) at the end of CCR. There were significant but weak-to-moderate correlations between IMT and VWV (r = 0.25, p = .01), IMT and TPV (r = 0.21, p = .01), TPV and TPA (r = 0.60, p < .0001) and VWV and TPV (r = 0.22, p = .02). Subjects with improved TC/HDL ratios showed improved carotid VWV although, this was not statistically significant.ConclusionIn this preliminary evaluation, there were no significant differences in carotid US measurements in the control or CCR group; a larger sample size and/or longer duration is required to detect significant changes in US or other risk factor measurements.

Second-order Texture Measurements of 3He Ventilation MRI:

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.

Pulmonary imaging abnormalities in an adult case of congenital lobar emphysema.

Congenital lobar emphysema is mainly diagnosed in infants, although rare cases are reported in adults. A 20-yr-old female with acute dyspnea, chest pain and left upper lobe (LUL) chest x-ray hyperlucency underwent 3He magnetic resonance imaging (MRI) for ventilation and apparent diffusion coefficient (ADC) measurements, as well as CT for emphysema and airway wall measurements. Forced expiratory volume in 1s, residual volume, and airways-resistance were abnormal, but there was normal carbon-monoxide-diffusing-capacity. The LUL relative area of the density histogram <-950 HU and airway morphology were highly abnormal compared with the other lobes and coincident with highly abnormal MRI-derived acinar duct dimensions. CT also identified bronchial atresia and congenital lobar emphysema as the source of symptoms in this case where there was also functional imaging evidence of collateral ventilation from the fissure (and not the abnormally terminated airway) into the emphysematous LUL.