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The purpose of this study was to extend established methods for fractional ventilation mapping using 19F 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. 19F 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, 19F 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. Copyright © 2016 John Wiley & Sons, Ltd.

MRI of hyperpolarized 129Xe gas and 13C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized 129Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (Ttr) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-13C]pyruvate. In this work, the application of hyperpolarized 129Xe and 13C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, Ttr and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis. Copyright © 2014 John Wiley & Sons, Ltd.

Fluorine-19 ((19)F) MRI of the lungs using inhaled inert fluorinated gases can potentially provide high quality images of the lungs that are similar in quality to those from hyperpolarized (HP) noble gas MRI. Inert fluorinated gases have the advantages of being nontoxic, abundant, and inexpensive compared with HP gases. Due to the high gyromagnetic ratio of (19)F, there is sufficient thermally polarized signal for imaging, and averaging within a single breath-hold is possible due to short longitudinal relaxation times. Therefore, the gases do not need to be hyperpolarized prior to their use in MRI. This eliminates the need for an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the lungs has been previously demonstrated in animals, and more recently in healthy volunteers and patients with lung diseases. The ongoing improvements in image quality demonstrate the potential of (19)F MRI for visualizing the distribution of ventilation in human lungs and detecting functional biomarkers. In this brief review, the development of inert fluorinated gas MRI, current progress, and future prospects are discussed. The current state of HP noble gas MRI is also briefly discussed in order to provide context to the development of this new imaging modality. Overall, this may be a viable clinical imaging modality that can provide useful information for the diagnosis and management of chronic respiratory diseases.

Lung ventilation was mapped in five healthy Brown Norway rats (210–377 g) using both hyperpolarized 3He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with 3He MRI were not significantly different from those obtained from Xe-CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two-tailed paired t-test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the 3He MRI method was found to be 0.17 ± 0.04 cm−1, whereas the average S/I gradient obtained using the Xe-CT method was found to be 0.016 ± 0.005 cm−1. In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two-tailed paired t-test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality. Copyright © 2011 John Wiley & Sons, Ltd.

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.

Fluorine-19 ((19)F) MRI of the lungs using inhaled inert fluorinated gases can potentially provide high quality images of the lungs that are similar in quality to those from hyperpolarized (HP) noble gas MRI. Inert fluorinated gases have the advantages of being nontoxic, abundant, and inexpensive compared with HP gases. Due to the high gyromagnetic ratio of (19)F, there is sufficient thermally polarized signal for imaging, and averaging within a single breath-hold is possible due to short longitudinal relaxation times. Therefore, the gases do not need to be hyperpolarized prior to their use in MRI. This eliminates the need for an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the lungs has been previously demonstrated in animals, and more recently in healthy volunteers and patients with lung diseases. The ongoing improvements in image quality demonstrate the potential of (19)F MRI for visualizing the distribution of ventilation in human lungs and detecting functional biomarkers. In this brief review, the development of inert fluorinated gas MRI, current progress, and future prospects are discussed. The current state of HP noble gas MRI is also briefly discussed in order to provide context to the development of this new imaging modality. Overall, this may be a viable clinical imaging modality that can provide useful information for the diagnosis and management of chronic respiratory diseases.

MRI of hyperpolarized (129)Xe gas and (13)C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized (129)Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (T(tr)) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-(13)C]pyruvate. In this work, the application of hyperpolarized (129)Xe and (13)C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, T(tr) and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis.

Lung ventilation was mapped in five healthy Brown Norway rats (210-377 g) using both hyperpolarized (3)He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with (3)He MRI were not significantly different from those obtained from Xe-CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two-tailed paired t-test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the (3)He MRI method was found to be 0.17 ± 0.04 cm(-1) , whereas the average S/I gradient obtained using the Xe-CT method was found to be 0.016 ± 0.005 cm(-1) . In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two-tailed paired t-test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality.

Lung ventilation was mapped in five healthy Brown Norway rats (210-377 g) using both hyperpolarized (3)He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with (3)He MRI were not significantly different from those obtained from Xe-CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two-tailed paired t-test was performed for each region, yielding p 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the (3)He MRI method was found to be 0.17 ± 0.04 cm(-1) , whereas the average S/I gradient obtained using the Xe-CT method was found to be 0.016 ± 0.005 cm(-1) . In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two-tailed paired t-test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality.

In this study, the upper-limit volume (gas plus partial tissue volume) as well as absolute volume (gas only) of lungs measured with hyperpolarized 3He-MR imaging is compared with that determined by micro-computed tomography (CT) under similar ventilation conditions in normal rats. Five Brown Norway rats (210–259 g) were ventilated with O2, alternately with 3He, using a computer-controlled ventilator, and 3D density-weighted images of the lungs were acquired during a breath hold after six wash-in breaths of 3He. The rats were then transferred to a micro-CT scanner, and a similar experimental setup was used to obtain images of the lungs during a breath hold of air with an airway pressure equal to that of the MR imaging breath hold. The upper-limit and absolute volumes obtained from 3He-MR and micro-CT methods were not significantly different (p > 0.05). The good agreement between the lung volumes measured with the two imaging methods suggests that 3He-MR imaging can be used for quantitative analysis of lung volume changes in longitudinal studies without the exposure to the ionizing radiation which accompanies micro-CT imaging. Copyright © 2010 John Wiley & Sons, Ltd.