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.
Diffusion and lung morphometry imaging using hyperpolarized gases are promising tools to quantify pulmonary microstructure noninvasively in humans and in animal models. These techniques assume the motion encoded is exclusively diffusive gas displacement, but the impact of cardiac motion on measurements has never been explored. Furthermore, although diffusion morphometry has been validated against histology in humans and mice using 3 He, it has never been validated in mice for 129 Xe. Here, we examine the effect of cardiac motion on diffusion imaging and validate 129 Xe diffusion morphometry in mice. Theory and Methods: Mice were imaged using gradient-echo-based diffusion imaging, and apparent diffusion-coefficient (ADC) maps were generated with and without cardiac gating. Diffusion-weighted images were fit to a previously developed theoretical model using Bayesian probability theory, producing morphometric parameters that were compared with conventional histology. Results: Cardiac gating had no significant impact on ADC measurements (dualgating: ADC = 0.020 cm 2 /s, single-gating: ADC = 0.020 cm 2 /s; P = .38). Diffusion-morphometry-generated maps of ADC (mean, 0.0165 ± 0.0001 cm 2 /s) and acinar dimensions (alveolar sleeve depth [h] = 44 µm, acinar duct radii [R] = 99 µm, mean linear intercept [L m ] = 74 µm) that agreed well with conventional histology (h = 45 µm, R = 108 µm, L m = 63 µm). Conclusion: Cardiac motion has negligible impact on 129 Xe ADC measurements in mice, arguing its impact will be similarly minimal in humans, where relative cardiac
The purpose of this study was to determine which implementations of a T2-weighted fast spin-echo sequence of the liver resulted in observer preference in normal subjects. Five volunteers were scanned with a series of fast spin-echo sequences modified to allow for flow compensation, respiratory triggering (RT), ECG triggering, randomized phase encoding (RPE), breath-holding, and echo train length (ETL). Images were compared with conventional 2500/40/80 msec spin-echo images using flow compensation and spatial presaturation by two observers blinded to the specific sequence parameters. All FSE sequences were completed in less than the 12 minutes necessary to perform a conventional spin-echo sequence. The most preferred fast spin-echo sequence employed flow compensation, RT, and used an 8 ETL. Analysis of image preference, signal to noise, and contrast to noise showed that RT was the single most important variable in determining each image response (P < .01, P < .02, P < .01, respectively). There was some evidence that images obtained with an 8 ETL were preferred over those using a 16 ETL (P = .07). No other variables approached statistical significance although one reader preferred images with flow compensation in the frequency direction to those either not flow compensated or flow compensated in the slice direction. Respiratory triggered fast spin-echo images combined with flow compensation in the frequency direction and using ETL = 8 can provide image quality equal to conventional spin-echo sequences with significant time savings.
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