Validating in vivo hyperpolarized ¹²⁹Xe diffusion MRI and diffusion morphometry in the mouse lung

Abstract

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

In vivo methods and applications of xenon-129 magnetic resonance

“…Strong correlations were observed between histologically derived mean linear intercept and cylindrical geometry parameters. Furthermore, good agreement (10–30 µm difference) was observed between 129 Xe MR-derived Lm and mean linear intercept from histology [218] , [316] .…”

“…129 Xe ADC measurements are highly repeatable in COPD patients [157] , and demonstrate excellent linear correlation with 3 He ADC across a range of microstructural length scales [157] , [159] , [185] , [315] , indicating that 129 Xe ADC mapping is a robust methodology for imaging the lung microstructure. Importantly, 129 Xe ADC acquired from explanted human [190] and animal [191] , [192] , [316] lungs are significantly correlated with histologically derived mean linear intercept (Lm), a widely accepted measure of airspace size. Whilst the ADC value is sensitive to changes in alveolar dimensions, the measured ADC is also dependent upon experimental acquisition parameters such as B 0 field strength [193] , and diffusion-encoding pulsed gradient strength, orientation and timing [194] , [195] , [196] .…”

“…However, the validation of 129 Xe lung morphometry measurements derived from theoretical gas models against gold standard methods for morphometry measurement (namely, histology) has to date been restricted to preclinical studies. For example, 129 Xe lung morphometry measurements from the cylindrical geometry model were compared to histology in healthy mice lungs [316] , and in rat lungs instilled with disease models of emphysema and radiation-induced lung injury [217] , [218] , [219] . Strong correlations were observed between histologically derived mean linear intercept and cylindrical geometry parameters.…”

Dynamic evaluation of acute lung injury using hyperpolarized 129Xe magnetic resonance

“…Moreover, by using the technique of chemical shift saturation recovery (CSSR) MR spectroscopy (MRS), gas exchange functional parameters at the alveolar-capillary interface can be obtained. [14][15][16][17][18] Xe MR has been used to evaluate the impaired gas exchange function caused by ALI. 19 However, this important technique has not yet been employed for evaluating the dynamic physiological changes in the progression of ALI, especially the gas exchange function, which is critical for the treatment and management of ALI in the clinic.…”

Protocols for multi‐site trials using hyperpolarized 129Xe MRI for imaging of ventilation, alveolar‐airspace size, and gas exchange: A position paper from the 129Xe MRI clinical trials consortium

“…Alternatively, advanced diffusion weighted imaging can be combined with a theoretical model of the pulmonary geometry or a mathematical model of diffusion behavior to calculate lung morphometry parameters 61,64,65 ; this requires acquiring additional b‐values at the expense of longer scan times or reduced spatial resolution. Such diffusion morphometry techniques have been well‐validated in animals, humans, and realistic airway geometries 28,29,66‐70 …”