Chronic
obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)
are heterogeneous diseases with different features and phenotypes. Accordingly, one goal is the
development of ways to identify regional lung structure and function in these patients
to improve patient care and outcomes. Although forced vital capacity is
validated for the assessment of COPD and IPF progression and prediction of
mortality, the need for tests that are more sensitive to pathophysiological
change in the lungs is well recognized for earlier diagnosis, longitudinal
assessment and for better markers of therapy and prognosis.
Chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF) are heterogeneous diseases with different features and phenotypes [1]. Accordingly, one goal is the development of ways to identify regional lung structure and function in these patients to improve patient care and outcomes. Although forced vital capacity is validated for the assessment of COPD and IPF progression and prediction of mortality, the need for tests that are more sensitive to pathophysiological change in the lungs is well recognized for earlier diagnosis, longitudinal assessment and for better markers of therapy and prognosis [2].
Different modalities using ionizing radiation for imaging of regional lung ventilation have been used, such as xenon (Xe)-enhanced computed tomography (CT)[3], single-photon emission CT with Xe, and nitrogen 13 positron emission tomography. Alternatively, pulmonary magnetic resonance (MR) imaging can be used without ionizing radiation to image regional lung ventilation. Several proton-based as well as multinuclear techniques have been of considerable research interest in recent years, such as oxygen-enhanced proton (1H) MR imaging and dynamic proton MR imaging of the lung. However, the contrast mechanisms quantifying regional ventilation are still under debate and require more validation [4-6]. Lung MR imaging of hyperpolarized gas tracers such as helium 3 (3He) and xenon 129 (129Xe) allows imaging of the respiratory tract with high spatial resolution at a high signal-to-noise ratio (SNR) [7]. Hyperpolarized gas MR imaging is usually performed in a single breath hold after inhalation of approximately 250–500 mL of gas. However, because of slow gas wash-in in patients with COPD, regional ventilation may not be quantified in regions of slow gas wash-in kinetics because of the initial lack of gas in partially obstructed lung segments. Gas washout has been measured during multiple breaths after a single inhalation of hyperpolarized 3He gas [8]. However, multibreath imaging of hyperpolarized gases must be corrected for radiofrequency depolarization and oxygen-induced relaxation.
Unlike 3He, 129Xe
is cheaper and readily available so has wider clinical potential. Xenon’s
solubility and unique spectral signature from its environment, either as gas in
the alveoli, when dissolved in the interstitial tissue, or taken up by the red
blood cells in the capillaries, make it particularly interesting for measuring
diffusion limitation. Previous studies with 129Xe magnetic
resonance spectroscopy have focused on whole lung measurements of the dynamics
of the xenon signals from the tissue, blood and airspaces, in order to
estimate the interstitial barrier thickness and have shown differences between
healthy and IPF lungs[9, 10].
Functional lung MR imaging of thermally polarized fluorinated gas tracers (eg, sulfur hexafluoride [SF6], hexafluoroethane [C2F6], and perfluoropropane [C3F8]) is a potential alternative to hyperpolarized gases. Because of the large gyromagnetic ratio of fluorine 19 (19F) and the rapid signal recovery after radiofrequency excitation of fluorinated gases (T1 <20 msec), 19F gas MR imaging can be performed with a reasonable SNR even with thermally polarized gas. In addition, because fluorinated gases are chemically inert, they do not diffuse into the blood after inhalation and can be mixed with oxygen with negligible effect on its MR imaging signal behavior. Thus, a normoxic 19F gas mixture can be continuously inhaled over several minutes without any notable adverse effects. Inhaling a mixture of the 19F tracer gas and oxygen over several minutes may provide quantitative regional information of lung ventilation even in regions of slow gas wash-in or washout kinetics. However, the major challenge of lung MR imaging by using fluorinated gas tracers is the relatively low SNR compared with that of hyperpolarized 129Xe gas MR imaging [11-13].
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