Peter J. Niedbalski, Ph.D., Zackary I. Cleveland, Ph.D.
Peter J. Niedbalski, Ph.D., Zackary I. Cleveland, Ph.D.
Department of Internal Medicine, University of Kansas Medical Center, Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center
ABSTRACT:
Characterizing lung function is vital in assessing diseasing state, understanding disease pathophysiology, and monitoring therapies. However, current clinical methods of evaluating lung function, such as spirometry, have several limitations, including effort dependence and lack of regional information. Hyperpolarized (HP) 129Xe MRI enables imaging of pulmonary structure and function non-invasively and with no ionizing radiation. In HP 129Xe MRI, the nuclear polarization of xenon gas is enhanced >100,000-fold. Then, a subject is asked to inhale the highly polarized gas which is then imaged during a short (<16s) breath hold. Different imaging techniques enable the regional quantification of ventilation, gas diffusion, and gas exchange. Each of these methods has shown sensitivity to disease state in wide variety of pulmonary diseases, including COPD, Cystic Fibrosis, Asthma, Pulmonary Hypertension, and Idiopathic Pulmonary Fibrosis.
Preclinical Imaging using Hyperpolarized 129Xe MRI
Figure 1. Mice are imaged using a home-build, hyperpolarized gas-compatible ventilator. Animals are intubated, placed in the 3D-printed cradle, and ventilated with hyperpolarized xenon. [1]
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Figure 2.
Because small animals are unable to hold their breath long enough to fully encode an image, small subsets of images are acquired with every inhalation of xenon. Images are then reconstructed, creating an image representing a time average over the entire imaging window. Typically, images are acquired using 3D volumetric imaging sequences, such as 3D radial (left). However, the imaging time can be dramatically reduced with minimal loss of quality by using spiral image encoding (right).
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Figure 3.
By applying diffusion weighting to hyperpolarized xenon imaging in mice (a), the apparent diffusion coefficient (ADC, b) of hyperpolarized 129Xe within the pulmonary microstructure can be imaged, providing insight into alveolar dimensions. By combining diffusion imaging with a geometric model of the pulmonary microstructure, morphometric parameters can be obtained non-invasively, including alveolar number density (c), alveolar sleeve depth (h, d), acinar duct radius (R, e), and mean linear intercept (Lm, f). [2]
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Figure 4.
Ventilation imaging during a breath-hold shows clear differences between a healthy subject (top) and an individual with cystic fibrosis (bottom) (a). Through careful choice of imaging sequence, the decay of hyperpolarized signal can be mapped with no extra data collection (b), allowing for calculation of overall signal attenuation (c) and quantitatively corrected images (d). [3]
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CONCLUSIONS:
Hyperpolarized 129Xe is an effective method for imaging pulmonary structure and function in both preclinical models and in human patients.
• Ventilation imaging shows the regional distribution of gas within the lungs and can show regions that are not ventilating properly
• Diffusion imaging provides insight into the pulmonary microstructure, and combined with a geometric model, can provide morphometric parameters non-invasively.
• Gas exchange imaging provides regional information regarding the gas transfer from the alveoli, through the interstitium, and into red blood cells.
REFERENCES:
1 Niedbalski PJ et al NMR in Biomedicine 2020 33 7 e 4302
2 Niedbalski PJ, et al Magn Reson Med Accepted Sep 14 2020
3 Niedbalski PJ, et al Magn Reson Med 2019 82 1 367 376
4 Niedbalski PJ, et al J Appl Physiol 2020 129 2 218 219
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