A portable ventilator with integrated physiologic monitoring for hyperpolarized 129Xe MRI in rodents

Abstract

Hyperpolarized (HP) Xe MRI is emerging as a powerful, non-invasive method to image lung function and is beginning to find clinical application across a range of conditions. As clinical implementation progresses, it becomes important to translate back to well-defined animal models, where novel disease signatures can be characterized longitudinally and validated against histology. To date, preclinicalXe MRI has been limited to only a few sites worldwide with 2D imaging that is not generally sufficient to fully capture the heterogeneity of lung disease. To address these limitations and facilitate broader dissemination, we report on a compact and portable HP gas ventilator that integrates all the gas-delivery and physiologic monitoring capabilities required for high-resolution 3D hyperpolarized Xe imaging. This ventilator is MR- and HP-gas compatible, driven by inexpensive microcontrollers and open source code, and allows for precise control of the tidal volume and breathing cycle in perorally intubated mice and rats. We use the system to demonstrate data acquisition over multiple breath-holds, during which lung motion is suspended to enable high-resolution 3D imaging of gas-phase and dissolved-phaseXe in the lungs. We demonstrate the portability and versatility of the ventilator by imaging a mouse model of lung cancer longitudinally at 2 Tesla, and a healthy rat at 7 Tesla. We also report the detection of subtle spectroscopic fluctuations in phase with the heart rate, superimposed onto larger variations stemming from the respiratory cycle. This ventilator was developed to facilitate duplication and gain broad adoption to accelerate preclinical Xe MRI research.

Preclinical hyperpolarized 129Xe MRI: ventilation and T2* mapping in mouse lungs at 7 T using multi‐echo flyback UTE

“…MRI of hyperpolarized (HP) noble gases ( 129 Xe and 3 He) has emerged as a powerful tool to image ventilation, diffusive gas exchange, and airspace dimensions within the lungs in both human subjects and preclinical models 1,2 . However, the quantitative accuracy of HP gas images is significantly reduced by the transient nature of the HP longitudinal magnetization.…”

“…Similarly, T 1 decay can be mitigated in human studies through the use of efficient sequences such as spiral ones 8,9 . However, for rodent imaging, common practice is to mechanically ventilate animals and collect only a small sub‐sample of k ‐space with each breath, with k ‐space being fully encoded over a large number of breaths 1,10 . This method, which continuously cycles fresh HP gas in/out of the lungs, effectively avoids the effect of T 1 in vivo, because the relaxational timescale ( T 1 ~ 30 s) 5,11 is long relative to the breath‐hold time in rodents (<500 ms) 12 .…”

Improved preclinical hyperpolarized 129Xe ventilation imaging with constant flip angle 3D radial golden means acquisition and keyhole reconstruction

“…Given its utility in measuring both lung structure and function at high resolution, HP gas MRI is likewise gaining traction as a preclinical tool for quantitative imaging of animal models of human disease 2–10 . In contrast to human imaging, where images are usually acquired in a single breath‐hold, preclinical imaging in small animals is most commonly accomplished by mechanically ventilating animals with HP gas and encoding k‐space over a large number of breaths 2,3,5 . As a result, magnetization does not decay monotonically as it does in human HP gas imaging, but rather, it displays a repeated pattern of replenishment and decay over tens to hundreds of breaths 11 …”

“…Despite its advantages, 3D radial imaging suffers from inefficient coverage of k‐space. Thus, to acquire images in a reasonable time and with a reasonable amount of HP gas, multiple projections must be acquired per breath 2 . In standard human imaging, the need to fully acquire k‐space within a single breath leads to the use of small RF flip angles.…”

A Novel System for Patient Ventilation and Dosing of Hyperpolarized 3He for Magnetic Resonance Imaging of Human Lungs

“…These results opened new possibilities for the application of the technique in medical diagnostics, and stimulated the development of dedicated ventilators with the noble gas administration capability. A detailed description of a device modified for small animal studies was given in [18][19][20]. It was followed by a fully scalable system that could be used for humans [21], and a sophisticated ventilation system dedicated to MRI of human lungs with the use hyperpolarized noble gases [22].…”