Trine Stavngaard

Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial

The aim of the present study was to apply hyperpolarised (HP) 3He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and α1-antitrypsin deficiency (α1-ATD) from healthy volunteers and compare HP 3He MRI findings with high-resolution computed tomography (HRCT) in a multicentre study. Quantitative measurements of HP 3He MRI (apparent diffusion coefficient (ADC)) and HRCT (mean lung density (MLD)) were correlated with pulmonary function tests. A prospective three centre study enrolled 122 subjects with COPD (either acquired or genetic) and age-matched never-smokers. All diagnostic studies were completed in 94 subjects (52 with COPD; 13 with α1-ATD; 29 healthy subjects; 63 males; and 31 females; median age 62 yrs). The consensus assessment of radiologists, blinded for other test results, estimated nonventilated lung volume (HP 3He MRI) and percentage diseased lung (HRCT). Quantitative evaluation of all data for each centre consisted of ADC (HP 3He MRI) and MLD measurements (HRCT), and correlation with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) indicating airway obstruction, and the diffusing capacity of the lung for carbon monoxide (DL,CO) indicating alveolar destruction. Using lung function tests as a reference, regional analysis of HP 3He MRI and HRCT correctly categorised normal volunteers in 100% and 97%, COPD in 42% and 69% and α1-ATD in 69% and 85% of cases, respectively. Direct comparison of HP 3He MRI and CT revealed 23% of subjects with moderate/severe structural abnormalities had only mild ventilation defects. In comparison with lung function tests, ADC was more effective in separating COPD patients from healthy subjects than MLD (p<0.001 versus 0.038). ADC measurements showed better correlation with DL,CO than MLD (r = 0.59 versus 0.29). Hyperpolarised 3He MRI correctly categorised patients with COPD and normal volunteers. It offers additional functional information, without the use of ionising radiation whereas HRCT gives better morphological information. We showed the feasibility of a multicentre study using different magnetic resonance systems.

Assessment of lung microstructure with magnetic resonance imaging of hyperpolarized Helium-3☆

Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are shown.

Hyperpolarised 3He MRI and 81mKr SPECT in chronic obstructive pulmonary disease

PurposeDuring recent years, magnetic resonance imaging (MRI) using hyperpolarised (HP) 3He gas has emerged as a promising new method for the imaging of lung ventilation. However, systematic comparisons with nuclear medicine techniques have not yet been performed. The aim of this study was to compare ventilation imaging methods in 26 patients with chronic obstructive pulmonary disease (COPD) and nine lung healthy volunteers.MethodsHP 3He MRI, 81mKr single-photon emission computed tomography (SPECT), high-resolution computed tomography (HRCT) and pulmonary function tests were performed. The three scans were scored visually as percentage of non-ventilated/diseased lung, and a computer-based objective measure of the ventilated volume in HP 3He MRI and 81mKr SPECT and an emphysema index in HRCT were calculated.ResultsWe found a good correlation between HP 3He MRI and 81mKr SPECT for both visual defect score (r=0.80, p<0.0001) and objective estimate of ventilation (r=0.45, p=0.0157). In addition, both scans were well correlated with reference methods for the diagnosis of emphysema (pulmonary function test and HRCT). The defect scores were largest on 81mKr SPECT (the score on HP 3He MRI was one-third less than that on 81mKr SPECT), but the difference was reduced after normalisation for different breathing depths (HP 3He MRI at total lung capacity; 81mKr SPECT at tidal breathing at functional residual capacity).ConclusionHP 3He MRI provides detailed ventilation distribution images and defect scores are comparable on HP 3He MRI and 81mKr SPECT. Additionally, new insights into the regional pulmonary microstructure via the apparent diffusion coefficient measurements are provided by HP 3He MRI. HP 3He MRI is a promising new diagnostic tool for the assessment of ventilation distribution.

The Effect of Inhaled Corticosteroids on the Development of Emphysema in Smokers Assessed by Annual Computed Tomography

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 μ g bid, or placebo. COPD was defined as FEV1 ≤ 70% pred, FEV1/FVC ≤ 60% and no reversibility to β2-agonists and oral corticosteroids. The patients were followed for 2–4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15thpercentile density (PD15) and the relative area of emphysema at a threshold of −910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV1 was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was −1.12 g/L in the budesonide group and −1.81 g/L in the placebo group (p = 0.09); the annual increase in RA–910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV1 between ICS (−54 mL) and placebo (−56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Rapid Fall in Lung Density Following Smoking Cessation in COPD

Introduction: Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD. Material and methods: Thirty-six patients quit smoking out of 254 current smokers with COPD who were followed with annual CT and lung function tests (LFT) for 2–4 years as part of a randomised placebo-controlled trial of the effect of inhaled budesonide on CT-lung density. Lung density was expressed as the 15th percentile density (PD15) and relative area of emphysema below -910 HU (RA-910). From the time-trends in the budesonide and placebo groups the expected CT-lung densities at the first visit after smoking cessation were calculated by linear regression and compared to the observed densities. Results: Following smoking cessation RA-910 increased by 2.6% (p = 0.003) and PD15 decreased by −4.9 HU (p = 0.0002). Furthermore, changes were larger in the budesonide group than the placebo group (PD15: −7.1 vs −2.8 HU. RA-910 3.7% vs 1.7%). These differences were, however, not statistically significant. The LFT parameters (FEV1 and diffusion capacity) were not significantly influenced by smoking cessation. Conclusion: Inflammation partly masks the presence of emphysema on CT and smoking cessation results in a paradoxical fall in lung density, which resembles rapid progression of emphysema. This fall in density is probably due to an anti-inflammatory effect of smoking cessation.

Quantitative assessment of regional emphysema distribution in patients with chronic obstructive pulmonary disease (COPD)

Purpose: To compare objective and subjective assessment of the distribution of emphysema in unselected patients with chronic obstructive pulmonary disease (COPD). Material and Methods: 167 patients were computed tomography (CT) scanned, and the relative area (RA-910) of emphysema in each CT slice was plotted against table position. The craniocaudal distribution was calculated as the slope of the regression line, and grouped as upper-lung-zone predominance (ULP), lower-lung-zone predominance (LLP), or mild/homogeneous distribution (MHE). CT scans were also classified as ULP, LLP, and MHE based on visual assessment of three high-resolution CT (HRCT) slices, and the leading pattern of emphysema was classified as centrilobular (CLE), paraseptal (PSE), panlobular (PLE), or no emphysema (NE). Results: By objective classification, scans were divided into almost equal numbers of ULP, LLP, and MHE, whereas visual evaluation classified more scans as ULP (P<0.001) and very few as LLP (P<0.0001). In patients with CLE, 49% had ULP by objective classification, whereas LLP was the commonest leading pattern in PSE, PLE, and NE. Conclusion: We found significant discrepancies between the objective and subjective distributions of emphysema in various morphological patterns, which may be of clinical importance in, for instance, lung-volume-reduction surgery.

Alpha1-antitrypsin deficiency. 7: Computed tomographic imaging in alpha1-antitrypsin deficiency.

Computed tomographic scanning may replace lung function tests as the golden standard for assessing the response to known and novel treatments for α1-antitrypsin deficiency.

α1-Antitrypsin deficiency · 7: Computed tomographic imaging in α1-antitrypsin deficiency

Computed tomographic scanning may replace lung function tests as the golden standard for assessing the response to known and novel treatments for α1-antitrypsin deficiency.

Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He) Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

Background: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV1) being the most accepted and used measurement. However, FEV1 is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. Purpose: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) 3He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. Material and Methods: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP 3He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV1 and carbon monoxide lung diffusion capacity [DL,CO]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). Results: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP 3He MR scanning was 3.8% (0.014 cm2/s [SD 0.024 cm2/s]; not significant). The time trends for FEV1, DL,CO, CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and DL,CO (P<0.001). Conclusion: This pilot study indicates the possible use of nonionizing HP 3He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results.

Effects of Prostacyclin on Cerebral Blood Flow and Vasospasm After Subarachnoid Hemorrhage Randomized, Pilot Trial

Background and Purpose— Delayed ischemic neurological deficits (DINDs) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage. In this trial, we investigated the therapeutic potential of prostacyclin, an endogen substance with known effect on vascular tone and blood flow regulation, on factors related to DIND. Methods— This trial is a single-center, randomized, blinded, clinical, pilot trial with 3 arms. Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute, prostacyclin 2 ng/kg per minute, or placebo. The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10. Primary outcome was the difference in change from baseline in global cerebral blood flow. Secondary outcome measures were occurrence of DIND, angiographic vasospasm, and clinical outcome at 3 months. Results— No statistically significant difference in change of global cerebral blood flow was found between the intervention groups. The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group, although this difference was not statistically significant. No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups. Conclusions— Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible. Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range. It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01447095.