Application of a stretched-exponential model for morphometric analysis of accelerated diffusion-weighted 129Xe MRI of the rat lung.

OBJECTIVE: Diffusion-weighted, hyperpolarized 129Xe MRI is useful for the characterization of microstructural changes in the lung. A stretched exponential model was proposed for morphometric extraction of the mean chord length (Lm) from diffusion-weighted data. The stretched exponential model enables accelerated mapping of Lm in a single-breathhold using compressed sensing. Our purpose was to compare Lm maps obtained from stretched-exponential model analysis of accelerated versus unaccelerated diffusion-weighted 129Xe MRI data obtained from healthy/injured rat lungs. MATERIAL AND METHODS: Lm maps were generated using a stretched-exponential model analysis of previously acquired fully sampled diffusion-weighted 129Xe rat data (b values = 0 … 110 s/cm2) and compared to Lm maps generated from retrospectively undersampled data simulating acceleration factors of 7/10. The data included four control rats and five rats receiving whole-lung irradiation to mimic radiation-induced lung injury. Mean Lm obtained from the accelerated/unaccelerated maps were compared to histological mean linear intercept. RESULTS: Accelerated Lm estimates were similar to unaccelerated Lm estimates in all rats, and similar to those previously reported (< 12% different). Lm was significantly reduced (p < 0.001) in the irradiated rat cohort (90 ± 20 µm/90 ± 20 µm) compared to the control rats (110 ± 20 µm/100 ± 15 µm) and agreed well with histological mean linear intercept. DISCUSSION: Accelerated mapping of Lm using a stretched-exponential model analysis is feasible, accurate and agrees with histological mean linear intercept. Acceleration reduces scan time, thus should be considered for the characterization of lung microstructural changes in humans where breath-hold duration is short.

High spatial resolution hyperpolarized 3 He MRI of the rodent lung using a single breath X-centric gradient-recalled echo approach.

PURPOSE: Hyperpolarized (HP) gas MRI of the rodent lung is of great interest because of the increasing need for novel biomarkers with which to develop new therapies for respiratory diseases. The use of fast gradient-recalled echo (FGRE) for high-resolution HP gas rodent lung MRI is challenging as a result of signal loss caused by significant diffusion weighting, particularly in the larger airways. In this work, a modified FGRE approach is described for HP 3 He rodent lung MRI using a centric-out readout scheme (ie, x-centric), allowing high-resolution, density-weighted imaging. METHODS: HP 3 He x-centric imaging was performed in a phantom and compared with a conventional partial-echo FGRE acquisition for in-plane spatial resolutions varying between 39 and 312 µm. Partial-echo and x-centric acquisitions were also compared for high spatial-resolution breath-hold (1 s) imaging of rodent lungs. RESULTS: X-centric provided improved signal-to-noise ratio efficiency by a factor of up to 13/1.7 and 6.7/1.8, compared with the partial-echo FGRE for the airways/parenchyma of mouse and rat, respectively, at high spatial resolutions in vivo (<78 µm). In particular, rodent major airways with less restricted diffusion of 3 He could only be visualized with the x-centric method. CONCLUSIONS: The x-centric method significantly reduces diffusion weighting, allowing high spatial and temporal resolution HP 3 He gas density-weighted rodent lung MRI. Magn Reson Med 78:2334-2341, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

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

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.

Hyperpolarized and inert gas MRI: the future.

Magnetic resonance imaging (MRI) is a potentially ideal imaging modality for noninvasive, nonionizing, and longitudinal assessment of disease. Hyperpolarized (HP) agents have been developed in the past 20 years for MR imaging, and they have the potential to vastly improve MRI sensitivity for the diagnosis and management of various diseases. The polarization of nuclear magnetic resonance (NMR)-sensitive nuclei other than (1)H (e.g., (3)He, (129)Xe) can be enhanced by a factor of up to 100,000 times above thermal equilibrium levels, which enables direct detection of the HP agent with no background signal. In this review, a number of HP media applications in MR imaging are discussed, including HP (3)He and (129)Xe lung imaging, HP (129)Xe brain imaging, and HP (129)Xe biosensors. Inert fluorinated gas MRI, which is a new lung imaging technique that does not require hyperpolarization, is also briefly discussed. This technique will likely be an important future direction for the HP gas lung imaging community.

In vivo regional ventilation mapping using fluorinated gas MRI with an x-centric FGRE method.

PURPOSE: Inert fluorinated gas lung MRI is a new and promising alternative to hyperpolarized gas lung MRI; it is less expensive and does not require expensive isotopes/polarizers. The thermally polarized nature of signal obtained from fluorinated gases makes it relatively easy to use for dynamic lung imaging and for obtaining lung ventilation maps. In this study, we propose that the sensitivity and resolution of fluorine-19 (19F) in vivo images can be improved using the x-centric pulse sequence, thereby achieving a short echo time/pulse repetition time. This study is a transitional step for converting to more sustainable gases for lung imaging. METHODS: A 19F-resolution phantom was used to validate the efficiency of performing the x-centric pulse sequence on a clinical scanner. Ventilation maps were obtained in the lungs of five normal rats with a washout approach (adapted from Xe-enhanced computed tomography [Xe-CT] regional ventilation mapping), using mixtures of either sulfur hexafluoride/oxygen or perfluoropropane/oxygen and a two-breath x-centric method. RESULTS: Fractional ventilation (r) values obtained in this study (0.35-0.46 interval) were in good agreement with previously published values for 3He/129Xe. Calculated r gradients agreed well with published gradients obtained in rats with Xe-CT measurements. CONCLUSIONS: These results suggest that fluorinated gases can be reliably used in vivo in dynamic lung studies as an alternative to 3He/129Xe.

Inert fluorinated gas MRI: a new pulmonary imaging modality.

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.

Comparison of hyperpolarized (3)He MRI rat lung volume measurement with micro-computed tomography.

In this study, the upper-limit volume (gas plus partial tissue volume) as well as absolute volume (gas only) of lungs measured with hyperpolarized (3)He-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 O(2), alternately with (3)He, 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 (3)He. 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 (3)He-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 (3)He-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.

Rapid 3-D mapping of hyperpolarized 3He spin-lattice relaxation times using variable flip angle gradient echo imaging with application to alveolar oxygen partial pressure measurement in rat lungs.

OBJECTIVE: The purpose of this work was to develop a rapid 3-D, variable flip angle (VFA) method for measurement of hyperpolarized (3)He T(1) which accounts for the effects of radiofrequency (RF) pulses without the need for additional flip angle information. MATERIALS AND METHODS: The 3-D, VFA method was validated in vitro over a range of oxygen partial pressures ranging from 0.04 to 0.52 atm. The approach was also tested in vivo in five healthy rats as a function of increasing number of wash-out breaths. The T(1) accuracy of the VFA method in the presence of flip angle mis-setting and RF field non-uniformity was compared with the CFA method using simulations and experiments. RESULTS: T(1) measurements were found to provide p(A)O(2) estimates, both in vitro and in vivo consistent with those predicted based on gas dilution and/or ventilation para- meters. For the RF pulse mis-setting (4%) and RF field non-uniformity (3%) used here, the VFA method provided a T(1) accuracy of better than 5% compared to 12% for the CFA method. CONCLUSION: With sufficient RF field homogeneity (3%) and proper calibration (4%), the VFA approach can provide rapid and reliable 3-D T(1) mapping of hyperpolarized (3)He without the need for additional flip angle information.

Membrane gas diffusion measurements with MRI.

Gas transport across polymeric membranes is fundamental to many filtering and separation technologies. To elucidate transport mechanisms, and understand the behaviors of membrane materials, accurate measurement of transport properties is required. We report a new magnetic resonance imaging (MRI) methodology to measure membrane gas phase diffusion coefficients. The MRI challenges of low spin density and short gas phase relaxation times, especially for hydrogen gas, have been successfully overcome with a modified one-dimensional, single-point ramped imaging with T(1) enhancement, measurement. We have measured the diffusion coefficients of both hydrogen gas and sulfur-hexafluoride in a model polymeric membrane of potential interest as a gas separator in metal hydride batteries. The experimental apparatus is a modified one-dimensional diaphragm cell which permits measurement of the diffusion coefficient in experimental times of less than 1 min. The H(2) gas diffusion coefficient in the membrane was 0.54 +/- 0.01 mm(2)/s, while that of sulfur-hexafluoride was 0.14 +/- 0.01 mm(2)/s, at ambient conditions.

Thin film MRI-high resolution depth imaging with a local surface coil and spin echo SPI.

A multiple echo, single point imaging technique, employing a local surface coil probe, is presented for examination of thin film samples. Depth images with a nominal resolution of 5 microm were acquired with acquisition times on the order of 10 min. The method may be used to observe dynamic phenomenon such as polymerization, wetting, and drying in thin film samples. It is readily adapted to spatially resolved diffusion coefficient and T2 relaxation time mapping.