Progression of emphysema evaluated by MRI using hyperpolarized <sup>3</sup>he (hp <sup>3</sup>he) measurements in patients with alpha-1-antitrypsin (a1at) deficiency compared with CT and lung function tests

Stavngaard, Trine; Søgaard, Lise Vejby; Batz, Marion; Schreiber, Laura M.; Dirksen, Asger

doi:10.3109/02841850903213822

Cited by 17 publications

(12 citation statements)

References 34 publications

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“…Although the AATD patients and COPD ex-smokers were previously investigated by pioneers of diffusionweighted MRI using ADCs (44)(45)(46)(47), to our knowledge, this is the first direct comparison of morphometry modeling approaches across a wide spectrum of emphysema severity that is commonly observed in patients. This is important because both the extent and severity of emphysema differs significantly in elderly neversmokers and within patient subgroups, including those with smoking-related emphysema and patients with emphysema-related to AATD.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Ouriadov

Lessard

Sheikh

et al. 2017

Magnetic Resonance in Med

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Purpose: We generated lung morphometry measurements using single-breath diffusion-weighted MRI and three different acinar duct models in healthy participants and patients with emphysema stemming from chronic obstructive lung disease (COPD) and alpha-1 antitrypsin deficiency (AATD). Methods: Single-breath-inhaled 3 He MRI with five diffusion sensitizations (b-value ¼ 0, 1.6, 3.2, 4.8, and 6.4 s/cm 2 ) was used, and signal intensities were fit using a cylindrical and single-compartment acinar-duct model to estimate MRIderived mean linear intercept (L m ) and surface-to-volume ratio (S/V). A stretched exponential model was also developed to estimate the mean airway length and L m . Results: We evaluated 42 participants, including 15 elderly never-smokers (69 6 5 years), 12 ex-smokers without COPD (67 6 11 years), 9 COPD ex-smokers (80 6 6 years), and 6 AATD patients (59 6 6 years). In the never-and ex-smokers, the diffusing capacity of the lung for carbon monoxide (DL CO ) and computed tomography relative area of less than 2950 Hounsfield units (RA 950 ) were normal, but these were abnormal in the COPD and AATD patients, which is reflective of emphysema. Although cylindrical and stretched-exponential-model estimates of L m and S/V were not significantly different, the single-compartment-model estimates were significantly different (P < 0.05) for the never-and ex-smoker subgroups. All models estimated significantly worse L m and S/V in the AATD and COPD subgroups compared with the never-and exsmokers without emphysema. Conclusions: Differences in airspace enlargement may be estimated using L m and S/V, generated using MRI and a stretchedexponential or cylindrical model of the acinar ducts. Magn Reson Med 79:439-448,

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Section: Discussionmentioning

confidence: 99%

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Ouriadov

Lessard

Sheikh

et al. 2017

Magnetic Resonance in Med

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“…Apparent diffusion coefficients (ADCs) and respective maps of fully inflated lungs of healthy subjects are relatively homogeneous, and this uniformity is a hallmark of the normal lung, demonstrating regional confinement by the lungs' microstructure (6)(7)(8)(9). ADC maps in patients with emphysema have been shown to be nonuniform and to contain larger diffusion values (2,5,10,11), correlating well with the onset and progression of the disease, where the degree and location of destruction varies throughout the lung (8,(12)(13)(14)(15). Similarly, the choice of variables such as gradient strength, duration, and time between pulses to induce the diffusion sensitization has been shown to induce variability in the observed ADCs (14).…”

Section: Thoracic Imaging: Effect Of Lung Inflation Level On Apparentmentioning

confidence: 99%

Effect of Lung Inflation Level on Hyperpolarized³He Apparent Diffusion Coefficient Measurements in Never-Smokers

Halaweish¹,

Hoffman²,

Thedens³

et al. 2013

Radiology

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Purpose:To evaluate the effects of lung volume differences on apparent diffusion coefficient (ADC) measurements on a regional basis, with breath holds at volumes adjusted for differences in lung size across individuals according to the subject's vital capacity (VC). Materials and Methods:This study was approved by the local institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Imaging was performed under a physician's Investigational New Drug application from the Food and Drug Administration. ADC changes as a function of inflation levels were evaluated in 24 healthy never-smokers across three lung volumes (20%, 60%, and 100% VC) on the basis of the spirometric data collected from each subject. Response variables based on lung volume and anatomic position were assessed with multifactorial analysis of variance followed by posthoc pair-wise testing. Imaging was performed with a 1.5-T magnetic resonance (MR) unit with use of a two-dimensional gradient-echo fast low-angle shot sequence. Results:Significant differences in ADCs between lung volumes were observed for all inflation levels (20%, 60%, and 100% VC; P , .001), along with significant dependentnondependent vertical gradients at 20% VC (P , .0001) and 60% VC (P , .0001, left lung only). In addition, significant differences between mean values in the left and right lungs with respect to those in the whole lung were observed at the lower lung inflation levels (20% and 60% VC, P , .01), reaching more uniform expansion at 100% VC. Conclusion:The results confirm known anatomic differences in patterns of regional inflation and ventilation with corresponding lung volume changes, emphasizing the need for tight control over lung volume when performing hyperpolarized helium 3 ( He MR imaging is to be used to follow up small longitudinal changes in lung abnormalities.q RSNA, 2013

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“…However, lacunarity, a measure of the inhomogeneity in distribution of ADC values, did correlate with disease progression (Diaz et al, 2009). In a 2-year study in ␣1-antitrypsin-deficient patients, significant changes were reported for forced expiratory volume in 1 s, diffusion of CO, tissue density, and emphysema index from CT, but the increase in 3 He ADC values just missed significance (Stavngaard et al, 2009).…”

Section: Imaging In Respiratory Diseases: From Animal Models To Patientsmentioning

confidence: 99%

A View on Imaging in Drug Research and Development for Respiratory Diseases

Echteld¹,

Beckmann²

2011

J Pharmacol Exp Ther

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With the incidence of respiratory diseases increasing throughout the world, new therapies are needed. This review provides a short overview of different imaging techniques of interest for drug discovery and development within the pulmonary disease area. The focus is on studies performed in both animals and humans, which are of importance for understanding pathophysiological aspects and evaluating new drugs. Rather than emphasizing particular lung diseases, the noninvasive diagnosis and quantification of a number of characteristics related to several pathological conditions of the lung are addressed: inflammation, mucus secretion and clearance, emphysema, ventilation, perfusion, fibrosis, airway remodeling, and pulmonary arterial hypertension. Techniques are discussed based on their present use or potential future utilization in the context of drug studies.

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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

Abstract: This pilot study indicates the possible use of nonionizing HP (3)He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results.

Cited by 17 publications

References 34 publications

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Effect of Lung Inflation Level on Hyperpolarized³He Apparent Diffusion Coefficient Measurements in Never-Smokers

A View on Imaging in Drug Research and Development for Respiratory Diseases

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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

Abstract: This pilot study indicates the possible use of nonionizing HP (3)He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results.

Cited by 17 publications

References 34 publications

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha‐1 antitrypsin deficiency

Effect of Lung Inflation Level on Hyperpolarized3He Apparent Diffusion Coefficient Measurements in Never-Smokers

A View on Imaging in Drug Research and Development for Respiratory Diseases

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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

Effect of Lung Inflation Level on Hyperpolarized³He Apparent Diffusion Coefficient Measurements in Never-Smokers