Quantitative Assessment of Lung Ventilation and Microstructure in an Animal Model of Idiopathic Pulmonary Fibrosis Using Hyperpolarized Gas MRI

Stephen, Michael J.; Emami, Kiarash; Woodburn, John M.; Chia, Elaine; Kadlecek, Stephen; Zhu, Jie; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R.; Rossman, Milton D.

doi:10.1016/j.acra.2010.06.019

Cited by 23 publications

(23 citation statements)

References 37 publications

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“…On the other hand, the mean r values were less in bleomycin-instilled rats than in both the controls and LPS-instilled rats, but only significantly different from the control rats. Similarly, reduced fractional ventilation values were observed in a study involving fractional ventilation mapping using HP 3 He MRI in bleomycin-instilled rats, and it was suggested that a decrease in lung compliance was a major factor in diminishing alveolar expansion and ventilation (44). The fractional ventilation gradients from control rats agreed with expectations from the literature, where rats in the supine position had a greater ventilation in more dependent regions of the lung (34).…”

Section: Discussionsupporting

confidence: 80%

Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis

et al. 2016

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The purpose of this study was to extend established methods for fractional ventilation mapping using (19) F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. (19) F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O2 . Fractional ventilation maps were obtained using a wash-out approach, by switching the breathing mixture to pure O2 , and acquiring images following each successive wash-out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS-instilled rats and 0.19 ± 0.03 for bleomycin-instilled rats. Bleomycin-instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS-instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was -0.005 ± 0.008 cm(-1) for control rats, 0.013 ± 0.005 cm(-1) for LPS-instilled rats and 0.009 ± 0.018 cm(-1) for bleomycin-instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS-instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS- and bleomycin-instilled rats showed the opposite trend. Histology confirmed that LPS-instilled rats had a significantly elevated alveolar wall thickness, while bleomycin-instilled rats showed signs of substantial fibrosis. Overall, (19)F MRI may be able to detect the effects of pulmonary inflammation and fibrosis using a simple and inexpensive imaging approach that can potentially be translated to humans.

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Section: Discussionsupporting

confidence: 80%

Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis

et al. 2016

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“…An alternative method for identifying tissues at risk for disease progression is needed in order to better stage and triage patients eligible for emerging new therapies [212]. Initial efforts using HP 3 He MRI focused on the feasibility of measuring ventilation changes [213] to better detect early progression in fibrotic lung disease, but these efforts had limited success for several reasons. First, ventilation is secondary to the underlying process of fibrotic injury and therefore an indirect measure of severity; and second, few therapies were available to treat these patients beyond simply limiting environmental exposure.…”

Section: Applications Of Hyperpolarized Gas Mri To Pre-clinical Anmentioning

confidence: 99%

Magnetic resonance imaging with hyperpolarized agents: methods and applications

et al. 2017

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In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into 1) a brief introduction, 2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, 3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, 4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study 5) metabolic pathways in cancer and cardiac disease and 6) lung function in both pre-clinical and clinical research studies, 7) some future directions and challenges, and 8) an overall summary.

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“…Apparent diffusion coefficient (ADC) and fractional ventilation are commonly used metrics to evaluate lung function and structure. Hyperpolarized 3 He MRI analysis has shown that BLMor radiation-exposed rats had significantly decreased fractional ventilation and ADC of 3 He compared with control animals (23,24). Furthermore, areas of decreased ADC in radiation-treated rats correlated with lung fibrosis identified by histological analysis (24).…”

Section: Hyperpolarized Gas-enhanced Mrimentioning

confidence: 98%