Lindsay Mathew

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.

Chronic obstructive pulmonary disease: quantification of bronchodilator effects by using hyperpolarized ³He MR imaging.

PURPOSE To evaluate short-acting bronchodilator effects in chronic obstructive pulmonary disease (COPD) by using hyperpolarized helium 3 (³He) magnetic resonance (MR) imaging, spirometry, and plethysmography. MATERIALS AND METHODS Fourteen ex-smokers with COPD provided written informed consent to a local ethics board-approved and Health Insurance and Portability Accountability Act-compliant protocol and underwent hyperpolarized ³He and hydrogen 1 MR imaging, spirometry, and plethysmography before and a mean of 25 minutes ± 2 (standard deviation) after administration of 400 μg salbutamol. Distribution of ³He gas was evaluated by using semiautomated segmentation of ³He voxel intensities, where cluster 1 represented regions of signal void or ventilation defect volume (VDV), and clusters 2-5 (C2-C5) represented gradations of signal intensity from hypointensity (C2) to hyperintensity (C5). ³He ventilation defect percentage (VDP) was calculated as VDV normalized to the thoracic cavity volume. Comparisons of pre- and post-salbutamol means were performed by using a two-way mixed-design repeated measures analysis of variance, and comparisons of the magnitude of the treatment effect between pulmonary function and ³He MR imaging measurements were performed by using effect size (ES) calculations. The relationships between pulmonary function and ³He MR imaging findings were determined by using Spearman correlation coefficients. RESULTS After salbutamol administration, there were significant changes in forced expiratory volume in 1 second (FEV₁) (P = .001), total lung capacity (P = .04), and functional residual capacity (P = .03), as well as VDP (P < .0001) and ³He gas distribution (C2, P = .01; C3, P = .03; C4, P < .0001; and C5, P = .02). Treatment ES was greater for ³He VDP than for FEV(1) (0.50 vs 0.22). There was a significant correlation between baseline VDP and post-salbutamol FEV₁ change (r = -0.77, P = .001). Although five patients were classified as bronchodilator responders and nine patients were classified as bronchodilator nonresponders according to American Thoracic Society and European Respiratory Society criteria, there was no significant difference in the magnitude of the ³He MR imaging changes after salbutamol administration between responder groups. CONCLUSION ³He MR imaging depicted significant improvements in the distribution of ³He gas after bronchodilator therapy in ex-smokers with COPD with and those without clinically important changes in FEV₁.

Hyperpolarized 3He Functional Magnetic Resonance Imaging of Bronchoscopic Airway Bypass in Chronic Obstructive Pulmonary Disease

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was <12% predicted, and he was classified as an AB nonresponder. However, post-AB, he also demonstrated improvements in quality of life scores, 6 min walk distance and improvements in 3He gas distribution in the regions of stent placement. Given the complex relationship between well-established pulmonary function and quality of life measurements, the present case provides evidence of the value-added information functional imaging may provide in chronic obstructive pulmonary disease interventional studies.

Development and proof-of-concept of three-dimensional lung histology volumes

Most medical imaging is inherently three-dimensional (3D) but for validation of pathological findings, histopathology is commonly used and typically histopathology images are acquired as twodimensional slices with quantitative analysis performed in a single dimension. Histopathology is invasive, labour-intensive, and the analysis cannot be performed in real time, yet it remains the gold standard for the pathological diagnosis and validation of clinical or radiological diagnoses of disease. A major goal worldwide is to improve medical imaging resolution, sensitivity and specificity to better guide therapy and biopsy and to one day delay or replace biopsy. A key limitation however is the lack of tools to directly compare 3D macroscopic imaging acquired in patients with histopathology findings, typically provided in a single dimension (1D) or in two dimensions (2D). To directly address this, we developed methods for 2D histology slice visualization/registration to generate 3D volumes and quantified tissue components in the 3D volume for direct comparison to volumetric micro-CT and clinical CT. We used the elastase-instilled mouse emphysema lung model to evaluate our methods with murine lungs sectioned (5 μm thickness/10 μm gap) and digitized with 2μm in-plane resolution. 3D volumes were generated for wildtype and elastase mouse lung sections after semi-automated registration of all tissue slices. The 1D mean linear intercept (Lm) for wildtype (WT) (47.1 μm ± 9.8 μm) and elastase mouse lung (64.5 μm ± 14.0 μm) was significantly different (p<.001). We also generated 3D measurements based on tissue and airspace morphometry from the 3D volumes and all of these were significantly different (p<.0001) when comparing elastase and WT mouse lung. The ratio of the airspace-to-lung volume for the entire lung volume was also significantly and strongly correlated with Lm.

Hyperpolarized 3 He magnetic resonance pulmonary imaging: Image processing tools for clinical research

Hyperpolarized 3He magnetic resonance imaging has emerged as an in vivo imaging pulmonary research tool. It is unique among imaging methods in that it provides simultaneous lung structural and functional information at high resolution without the use of ionizing radiation, and thus is ideally suited for intensive serial longitudinal studies and for examining treatment effects. Despite the great promise of the method, currently, non-quantitative image analysis tools continue to be utilized for the analysis of functional images obtained from 3He MRI. In order for the translation of 3He MRI to clinical research, quantitative and precise image analysis tools are required. Thus, image processing tools for rigid and non-rigid registration, signal normalization and image subtraction are under development and being validated for the sensitive and specific measurement of airway and airspace changes in 3He MR image datasets.