Hyperpolarized 3He magnetic resonance imaging: Preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease

doi:10.1016/j.ejrad.2009.10.028

European Journal of Radiology

Volume 79, Issue 1, July 2011, Pages 140-146

https://doi.org/10.1016/j.ejrad.2009.10.028 Get rights and content

Abstract

Rationale and objectives

Emphysema and small airway obstruction are the pathological hallmarks of chronic obstructive pulmonary disease (COPD). The aim of this pilot study in a small group of chronic obstructive pulmonary disease (COPD) patients was to quantify hyperpolarized helium-3 (³He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for ³He MRI in detecting the lung structural and functional COPD phenotypes.

Materials and methods

We evaluated 20 ex-smokers with stage I (n = 1), stage II (n = 9) and stage III COPD (n = 10). All subjects underwent same-day plethysmography, spirometry, ¹H MRI and hyperpolarized ³He MRI at 3.0 T. ³He ventilation defect percent (VDP) was generated from ³He static ventilation images and ¹H thoracic images and the ³He apparent diffusion coefficient (ADC) was derived from diffusion-weighted MRI.

Results

Based on the relative contribution of normalized ADC and VDP, there was evidence of a predominant ³He MRI measurement in seven patients (n = 3 mainly ventilation defects or VDP dominant (VD), n = 4 mainly increased ADC or ADC dominant (AD)). Analysis of variance (ANOVA) showed significantly lower ADC for subjects with predominantly elevated VDP (p = 0.02 compared to subjects with predominantly elevated ADC; p = 0.008 compared to mixed group) and significantly decreased VDP for subjects with predominantly elevated ADC (p = 0.003, compared to mixed group).

Conclusion

In this small pilot study, a preliminary analysis shows the potential for ³He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.

Introduction

Chronic obstructive pulmonary disease (COPD) is the most common chronic, terminal respiratory disease worldwide and it continues to grow in prevalence [1] and yet has a very poor prognosis, despite aggressive therapy [1], [2], [3]. Although widespread pulmonary inflammation [4], [5] and diffuse lung tissue alterations are often observed [5], obstruction of the small airways (airways disease) and tissue destruction in the pulmonary parenchyma (emphysema) are the hallmark pathologies [6]. Accordingly, both airways disease and emphysema contribute to the clinical course of COPD, although the underlying mechanisms of both pathologies and the proportional contributions of these and their relationship outcomes are not completely understood.

The current functional definition of COPD [7] relies on the spirometric measurement of airflow obstruction. A fundamental limitation exists however, because the anatomy and physiology of the lung is complex and spirometry measurements reflect the global sum of all the different possible COPD pathologies including small airways disease, emphysema (i.e., parenchymal destruction), chronic bronchitis (i.e., large airway remodeling), and bronchiectasis (i.e., abnormal dilation of bronchi and bronchioles) [6].

The limitation of spirometry for differentiating between these pathologies or phenotypes has severely limited the scope of basic research and clinical studies that evaluate the relationship between these morphological phenotypes, disease pathogenesis, progression, and patient outcomes. Accordingly, one major goal of COPD research is to find a way to identify patients with these different underlying pathological “phenotypes”, which has the potential to have a profound effect on patient care and treatment options. In this regard, non-invasive high-resolution multi-detector X-ray computed tomography (CT) [8], [9], [10], [11] has been shown to detect unique and quantitative phenotypes of both emphysema and airway disease [12], [13], [14] with the potential to determine the contributions of both airway and airspace changes in COPD. Recent results suggest that CT-derived phenotypes provide evidence of underlying phenotype dominance in approximately 40% of subjects [12].

Hyperpolarized ³He magnetic resonance imaging (MRI) has emerged as research method that is complementary to CT because it allows for simultaneous visualization of tissue structure and regional airway function at high spatial and temporal resolution, without the use of ionizing radiation. In particular, the measurement of the ³He apparent diffusion coefficient (ADC) [15], which is a surrogate measurement of airspace size [16], [17], [18], [19], has been previously histologically validated [20] and correlated with CT measurements of emphysema [21]. Ventilation defects or signal voids in ³He spin density images are hypothesized to reflect airflow limitation related to airway narrowing or closure [22], but the exact pathology underlying ³He ventilation defects has yet to be determined. Importantly, both ³He MRI ADC and ventilation measurements have been shown to be highly reproducible [23], [24], [25], sensitive to age [26], [27], [28] and to disease-related changes [25], [29], [30], [31], [32].

Here we describe the results of a proof-of-principle and hypothesis-generating preliminary study where we explore the potential of hyperpolarized ³He MRI to classify (or phenotype) individual COPD ex-smokers based on the relative contributions of ventilation defect and ADC measurements. To our knowledge, this is the first study aimed at evaluating the potential for ³He MRI to detect phenotypes based on the proportional contributions of COPD structural and functional measurements.

Section snippets

Subjects

Twenty subjects were enrolled from the general population of the local tertiary health care center as well as directly from the COPD clinics at three local teaching hospitals. All subjects provided written informed consent to the study protocol approved by the local research ethics board and Health Canada and the study was compliant with both the Health Insurance Portability and Accountability Act (HIPAA, USA) and the Personal Information Protection and Electronic Documents Act (PIPEDA,

Study subjects

Baseline demographic characteristics are provided in Table 1 for the 20 subjects enrolled (13 male) by GOLD criteria [33]. A single subject presented with normal FEV₁ and low FEV₁/FVC (stage I) with a prior diagnosis of emphysema from thoracic CT. All other subjects were either categorized as GOLD stage II or stage III COPD according to post-bronchodilator spirometry performed on the same day as MRI. Mean body mass index (BMI) and BMI range for each subject subgroup was similar. As the COPD

Discussion

In this pilot study of COPD ex-smokers, we made a number of important observations that are relevant to the potential use of ³He MRI. First, although this was a relatively small pilot study, preliminary analysis showed that there was evidence of a single ³He measurement—either VDP or ADC providing the main contribution to ³He MRI measured disease. In particular, some patients reported high ADC and nearly normal ³He ventilation images with normal ADC based on age-matched healthy non-smoker

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¹: Imaging Research Laboratories, Robarts Research Institute, PO Box 5015, 100 Perth Drive, London, Canada N6A 5K8. Tel.: +1 519 663 5777x24107; fax: +1 519 931 5238.

²: Division of Emergency Medicine, London Health Sciences Center, University Hospital, 339 Windermere Road, London, Ontario, Canada N6A 5A5. Tel.: +1 519 663 3648; fax: +1 519 663 8803.

³: Imaging Research Laboratories, Robarts Research Institute, PO Box 5015, 100 Perth Drive, London, Canada N6A 5K8. Tel.: +1 519 663 5777x24325; fax: +1 519 931 5238.

⁴: London Health Sciences Centre - Victoria Hospital, 800 Commissioners Road East, London, Canada Ontario, N6A 4G5. Tel.: +1 519 667 6767; fax: +1 519 685 8406.

View full text

Hyperpolarized 3He magnetic resonance imaging: Preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease

Abstract

Rationale and objectives

Materials and methods

Results

Conclusion

Introduction

Section snippets

Subjects

Study subjects

Discussion

Lancet

Chest

Chest

Eur J Radiol

Tesla Acad Radiol

Acad Radiol

Tesla Acad Radiol

Eur J Radiol

J Allergy Clin Immunol

Ultrasound Med Biol

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative For Chronic Obstructive Lung Disease (GOLD) Workshop Summary

Am J Respir Crit Care Med

Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group

Ann Intern Med

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society

Am J Respir Crit Care Med

Site and nature of airway obstruction in chronic obstructive lung disease

N Engl J Med

The nature of small-airway obstruction in chronic obstructive pulmonary disease

N. Engl J Med

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary

Am J Respir Crit Care Med.

Significance of the relationship between lung recoil and maximum expiratory flow

J Appl Physiol

Comparison of computed density and macroscopic morphometry in pulmonary emphysema

Am J Respir Crit Care Med

A quantification of the lung surface area in emphysema using computed tomography

Am J Respir Crit Care Med

Hyperpolarized ³He magnetic resonance imaging: Preliminary evaluation of phenotyping potential in chronic obstructive pulmonary disease