Measurement of regional lung function in rats using hyperpolarized ³helium dynamic MRI

Abstract

Dynamic regional lung function was investigated in rats using a radial acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) 3 He gas delivered by a constant flow ventilator. Based on regional differences in the behavior of inspired air, the lung was conceptually divided into two regions (the major airways and the peripheral airspace) for purposes of functional analysis. To measure regional function in the major airways, a large RF flip angle (24°) was applied to reduce 3 He magnetization in the peripheral airspace, and signal intensity (SI) was normalized with the projected airway diameter to estimate local airflow. Higher normalized signal intensity was observed in the left branch airway as compared to the right branch airway. To determine regional function in the peripheral airspace, a small RF flip angle (6°) was used. Incremental increases of peripheral SI in successive lung images were consistent with the increase in lung volume. A new "skipping" scanning strategy using dummy frames allows a trade-off between the number of frames acquired for dynamic information, the RF flip angle, and the penetration depth of Over the past 40 years, measurements of inspired/expired airflow and pressure have been routinely used for pulmonary function testing in clinical applications. However, due to the limited accessibility of the lung for direct measurement, these techniques cannot determine regional lung function, which could be used to detect and locate lung abnormalities in their early stages. Recent studies demonstrated encouraging results in measuring regional lung function using hyperpolarized (HP) 3 He gas (1-6). Previously, we demonstrated the utility of a controlled delay to capture a single lung image at a desired time point of HP 3 He inspiration (7). More recently, we demonstrated the feasibility of using functional (dynamic) HP 3 He lung imaging on guinea pigs at microscopic resolution using a radial acquisition cine (RA-CINE) pulse sequence (8). In contrast to static imaging acquired at a single time point during a breath-hold, dynamic serial imaging acquired during inhalation provides time-course distributions of 3 He magnetization within the lung that may be indicative of regional lung function.In this study, we applied the RA-CINE pulse sequence with HP 3 He gas to explore this dynamic approach to measure regional lung function in rats. The lung was conceptually divided into two regions: 1) the major airways, which act as a conductive pipeline; and 2) the peripheral airspace, which acts as a reservoir. Ideally, in a coronal 3 He lung image, the signal intensity (SI) in the region of the major airways could be measured to indicate airflow, while that in the peripheral airspace could be measured to indicate ventilating volume. However, in the region of the major airways, the caliber of the airway plays a dominant role in determining the magnitude of the acquired signals in the coronal view. The SI in the large airway is understandably higher than that in the small airway. Thus, the SI...

Dynamic lung morphology of methacholine‐induced heterogeneous bronchoconstriction

“…In our previous study, we demonstrated that the airflow (velocity) in the major airways is proportional to the signal intensity normalized with projected airway diameter, as shown in the coronal 3 He dynamic images (14). In the current study, we investigated the airflow profile within the conducting airway after the MCh challenge (Table 1).…”

Dynamic lung morphology of methacholine‐induced heterogeneous bronchoconstriction

“…In our previous study, we demonstrated that the airflow (velocity) in the major airways is proportional to the signal intensity normalized with projected airway diameter, as shown in the coronal 3 He dynamic images (14). In the current study, we investigated the airflow profile within the conducting airway after the MCh challenge (Table 1).…”

Regional ventilation mapping of the rat lung using hyperpolarized 129Xe magnetic resonance imaging

“…To maintain the health and stability of the animal, the hyperpolarized gas will need to be mixed with O 2 . This concept has already been demonstrated previously with minimal depolarization of the hyperpolarized gas (23)(24)(25). Careful consideration must be given to calibration of O 2 tidal volumes, so that they are a consistent and reproducible fraction of the total gas delivered to the animal.…”

In vivo MRI using real‐time production of hyperpolarized 129Xe

“…This regulator was selected because its all-Teflon construction was expected to better retain 129 Xe polarization compared to conventional regulators containing steel components. The regulator's low-pressure output was routed using ¼” Perfluoroalkoxy (PFA) tubing (PFA-T4−047−100, Raleigh Valve & Fitting, Raleigh, NC) to an HP-gas compatible ventilator (16) where it replaced the typical Tedlar bag in a pressurized cylinder (17) that has become the standard for small animal HP gas delivery.…”

Dynamic lung morphology of methacholine‐induced heterogeneous bronchoconstriction

“…In our previous study, we demonstrated that the airflow (velocity) in the major airways is proportional to the signal intensity normalized with projected airway diameter, as shown in the coronal 3 He dynamic images (14). In the current study, we investigated the airflow profile within the conducting airway after the MCh challenge (Table 1).…”

Regional ventilation mapping of the rat lung using hyperpolarized 129Xe magnetic resonance imaging

“…To maintain the health and stability of the animal, the hyperpolarized gas will need to be mixed with O 2 . This concept has already been demonstrated previously with minimal depolarization of the hyperpolarized gas (23)(24)(25). Careful consideration must be given to calibration of O 2 tidal volumes, so that they are a consistent and reproducible fraction of the total gas delivered to the animal.…”

In vivo MRI using real‐time production of hyperpolarized 129Xe

“…This regulator was selected because its all-Teflon construction was expected to better retain 129 Xe polarization compared to conventional regulators containing steel components. The regulator's low-pressure output was routed using ¼” Perfluoroalkoxy (PFA) tubing (PFA-T4−047−100, Raleigh Valve & Fitting, Raleigh, NC) to an HP-gas compatible ventilator (16) where it replaced the typical Tedlar bag in a pressurized cylinder (17) that has become the standard for small animal HP gas delivery.…”

Dynamic lung morphology of methacholine‐induced heterogeneous bronchoconstriction

“…In our previous study, we demonstrated that the airflow (velocity) in the major airways is proportional to the signal intensity normalized with projected airway diameter, as shown in the coronal 3 He dynamic images (14). In the current study, we investigated the airflow profile within the conducting airway after the MCh challenge (Table 1).…”

Regional ventilation mapping of the rat lung using hyperpolarized 129Xe magnetic resonance imaging

“…To maintain the health and stability of the animal, the hyperpolarized gas will need to be mixed with O 2 . This concept has already been demonstrated previously with minimal depolarization of the hyperpolarized gas (23)(24)(25). Careful consideration must be given to calibration of O 2 tidal volumes, so that they are a consistent and reproducible fraction of the total gas delivered to the animal.…”

In vivo MRI using real‐time production of hyperpolarized 129Xe

“…This regulator was selected because its all-Teflon construction was expected to better retain 129 Xe polarization compared to conventional regulators containing steel components. The regulator's low-pressure output was routed using ¼” Perfluoroalkoxy (PFA) tubing (PFA-T4−047−100, Raleigh Valve & Fitting, Raleigh, NC) to an HP-gas compatible ventilator (16) where it replaced the typical Tedlar bag in a pressurized cylinder (17) that has become the standard for small animal HP gas delivery.…”