Mark S. Chawla

Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: Diffusion coefficient

In imaging of hyperpolarized noble gases, a knowledge of the diffusion coefficient (D) is important both as a contrast mechanism and in the design of pulse sequences. We have made diffusion coefficient maps of both hyperpolarized 3He and 129Xe in guinea pig lungs. Along the length of the trachea, 3He D values were on average 2.4 cm2/sec, closely reproducing calculated values for free gas (2.05 cm2/sec). The 3He D values measured perpendicular to the length of the trachea were approximately a factor of two less, indicating restriction to diffusion. Further evidence of restricted diffusion was seen in the distal pulmonary airspaces as the average 3He D was 0.16 cm2/sec. An additional cause for the smaller 3He D in the lung was due to the presence of air, which is composed of heavier and larger gases. The 129Xe results show similar trends, with the trachea D averaging 0.068 cm2/sec and the lung D averaging 0.021 cm2/sec. Magn Reson Med 42:721–728, 1999.

Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part II: T *(2).

The transverse relaxation time, T∗︁2, of hyperpolarized (HP) gas in the lung in vivo is an important parameter for pulse sequence optimization and image contrast. We obtained T∗︁2 maps of HP 3He and 129Xe in guinea pig lungs (n = 17) and in human lungs. Eight different sets of 3He guinea pig studies were acquired, with variation of slice selection, tidal volume, and oxygen level. For example, for a 3He tidal volume of 3 cm3 and no slice selection, the average T∗︁2 in the trachea was 14.7 ms and 8.0 ms in the intrapulmonary airspaces. The equivalent 129Xe experiment yielded an average T∗︁2 of 40.8 ms in the trachea and 18.5 ms in the intrapulmonary airspaces. The average 3He T∗︁2 in the human intrapulmonary airspaces was 9.4 ms. The relaxation behavior was predicted by treating the lung as a porous medium, resulting in good agreement between estimated and measured T∗︁2 values in the intrapulmonary airspaces. Magn Reson Med 42:729–737, 1999.

Functional MR microscopy of the lung using hyperpolarized 3He

A new strategy designed to provide functional magnetic resonance images of the lung in small animals at microscopic resolution using hyperpolarized 3He is described. The pulse sequence is based on a combination of radial acquisition (RA) and CINE techniques, referred to as RA‐CINE, and is designed for use with hyperpolarized 3He to explore lung ventilation with high temporal and spatial resolution in small animal models. Ventilation of the live guinea pig is demonstrated with effective temporal resolution of 50 msec and in‐plane spatial resolution of <100 μm using hyperpolarized 3He. The RA‐CINE sequence allows one to follow gas inflow and outflow in the airways as well as in the distal part of the lungs. Regional analysis of signal intensity variations can be performed and can help assess functional lung parameters such as residual gas volume and lung compliance to gas inflow. Magn Reson Med 41:787–792, 1999.

In vivo magnetic resonance vascular imaging using laser-polarized gas microbubbles

Laser-polarized gases (3He and 129Xe) are currently being used in magnetic resonance imaging as strong signal sources that can be safely introduced into the lung. Recently, researchers have been investigating other tissues using 129Xe. These studies use xenon dissolved in a carrier such as lipid vesicles or blood. Since helium is much less soluble than xenon in these materials, 3He has been used exclusively for imaging air spaces. However, considering that the signal of 3He is more than 10 times greater than that of 129Xe for presently attainable polarization levels, this work has focused on generating a method to introduce 3He into the vascular system. We addressed the low solubility issue by producing suspensions of 3He microbubbles. Here, we provide the first vascular images obtained with laser-polarized 3He. The potential increase in signal and absence of background should allow this technique to produce high-resolution angiographic images. In addition, quantitative measurements of blood flow velocity and tissue perfusion will be feasible.

Measurements of hyperpolarized gas properties in the lung. Part III: 3He T1

Hyperpolarized 3He spin‐lattice relaxation was investigated in the guinea pig lung using spectroscopy and imaging techniques with a repetitive RF pulse series. T1 was dominated by interactions with oxygen and was used to measure the alveolar O2 partial pressure. In animals ventilated with a mixture of 79% 3He and 21% O2, T1 dropped from 19.6 sec in vivo to 14.6 sec after cardiac arrest, reflecting the termination of the intrapulmonary gas exchange. The initial difference in oxygen concentration between inspired and alveolar air, and the temporal decay during apnea were related to functional parameters. Estimates of oxygen uptake were 29 ± 11 mL min−1 kg−1 under normoxic conditions, and 9.0 ± 2.0 mL min−1 kg−1 under hypoxic conditions. Cardiac output was estimated to be 400 ± 160 mL min−1 kg−1. The functional residual capacity derived from spirometric magnetic resonance experiments varied with body mass between 5.4 ± 0.3 mL and 10.7 ± 1.1 mL. Magn Reson Med 45:421–430, 2001.

Mixing oxygen with hyperpolarized 3He for small-animal lung studies

Hyperpolarized helium (HP 3He) is useful for direct MR imaging of the gas spaces of small animal lungs. Previously, breaths of 100% HP 3He were alternated with breaths of air to maximize helium signal in the lungs and to minimize the depolarizing effects of O2. However, for high‐resolution imaging requiring many HP 3He breaths (hundreds) and for pulmonary disease studies, a method was needed to simultaneously deliver O2 and HP 3He with each breath without significant loss of polarization. We modified our existing computer‐controlled ventilator by adding a plastic valve, additional relays and a controller. O2 and HP 3He are mixed at the beginning of each breath within the body of a breathing valve, which is attached directly to the endotracheal tube. With this mixing method, we found that T1 relaxation of HP 3He in the guinea pig lung was about 20 s compared to 30 s with alternate air/HP 3He breathing. Because imaging times during each breath are short (about 500 ms), the HP 3He signal loss from O2 contact is calculated to be less than 5%. We concluded that the advantages of mixing HP 3He with O2, such as shorter imaging times (reduced T1 losses in reservoir) and improved physiologic stability, outweigh the small signal loss from the depolarizing effects of oxygen on HP 3He. Copyright

Hyperpolarized 3He microspheres as a novel vascular signal source for MRI.

Hyperpolarized (HP) 3He can be encapsulated within biologically compatible microspheres while retaining sufficient polarization to be used as a signal source for MRI. Two microsphere sizes were used, with mean diameters of 5.3 ± 1.3 μm and 10.9 ± 3.0 μm. These suspensions ranged in concentration from 0.9–7.0% gas by volume. Spectroscopic measurements in phantoms at 2 T yielded 3He relaxation times that varied with gas concentration. At the highest 3He concentration, the spin‐lattice relaxation time, T1, was 63.8 ± 9.4 sec, while the transverse magnetization decayed with a time constant of T*2 = 11.0 ± 0.4 msec. In vivo MR images of the pelvic veins in a rat were acquired during intravenous injection of 3He microspheres (SNR ≈ 15). Advantages such as intravascular confinement, lack of background signal, and limited recirculation indicate quantitative perfusion measurements may be improved using this novel signal source. Magn Reson Med 43:440–445, 2000.