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

Fast apparent transverse relaxation (short T2 *) is a common obstacle when attempting to perform quantitative 1 H MRI of the lungs. While T2 * times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous 129 Xe), T2 * can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T2 * of HP 129 Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi-echo radial flyback imaging sequence and use it to measure HP 129 Xe T2 * at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T1 relaxation outside the animal by using multiple gradient-refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the 129 Xe T2 * in vivo for 10 healthy C57Bl/6 J mice and found T2 * ~ 5 ms in the lung airspaces. Interestingly, T2 * was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O2 content of the inhaled gas mixture. These results are discussed in the context of T2 * relaxation within porous media.

Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis.

Pulmonary fibrosis contributes to morbidity and mortality in a range of diseases, and there are no approved therapies for reversing its progression. To understand the mechanisms underlying pulmonary fibrosis and assess potential therapies, mouse models are central to basic and translational research. Unfortunately, metrics commonly used to assess murine pulmonary fibrosis require animals to be grouped and euthanized, increasing experimental difficulty and cost. We examined the ability of magnetic resonance imaging (MRI) to noninvasively assess lung fibrosis progression and resolution in a doxycycline (Dox) regulatable, transgenic mouse model that overexpresses transforming growth factor-α (TGF-α) under control of a lung-epithelial-specific promoter. During 7 wk of Dox treatment, fibrotic lesions were readily observed as high-signal tissue. Mean weighted signal and percent signal volume were found to be the most robust MRI-derived measures of fibrosis, and these metrics correlated significantly with pleural thickness, histology scores, and hydroxyproline content (R = 0.75-0.89). When applied longitudinally, percent high signal volume increased by 1.5% wk-1 (P < 0.001) and mean weighted signal increased at a rate of 0.0065 wk-1 (P = 0.0062). Following Dox treatment, lesions partially resolved, with percent high signal volume decreasing by -3.2% wk-1 (P = 0.0034) and weighted mean signal decreasing at -0.015 wk-1 (P = 0.0028). Additionally, longitudinal MRI revealed dynamic remodeling in a subset of lesions, a previously unobserved behavior in this model. These results demonstrate MRI can noninvasively assess experimental lung fibrosis progression and resolution and provide unique insights into its pathobiology.

Echo Decorrelation Imaging of Rabbit Liver and VX2 Tumor during In Vivo Ultrasound Ablation.

In open surgical procedures, image-ablate ultrasound arrays performed thermal ablation and imaging on rabbit liver lobes with implanted VX2 tumor. Treatments included unfocused (bulk ultrasound ablation, N = 10) and focused (high-intensity focused ultrasound ablation, N = 13) exposure conditions. Echo decorrelation and integrated backscatter images were formed from pulse-echo data recorded during rest periods after each therapy pulse. Echo decorrelation images were corrected for artifacts using decorrelation measured prior to ablation. Ablation prediction performance was assessed using receiver operating characteristic curves. Results revealed significantly increased echo decorrelation and integrated backscatter in both ablated liver and ablated tumor relative to unablated tissue, with larger differences observed in liver than in tumor. For receiver operating characteristic curves computed from all ablation exposures, both echo decorrelation and integrated backscatter predicted liver and tumor ablation with statistically significant success, and echo decorrelation was significantly better as a predictor of liver ablation. These results indicate echo decorrelation imaging is a successful predictor of local thermal ablation in both normal liver and tumor tissue, with potential for real-time therapy monitoring.

Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis.

BACKGROUND: Hyperpolarized 129Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. OBJECTIVE: To assess the feasibility, safety and tolerability of hyperpolarized 129Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. MATERIALS AND METHODS: Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent 129Xe MRI, receiving up to three doses of 129Xe gas prepared by either a commercially available or a homebuilt 129Xe polarizer. Subject heart rate and SpO2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. RESULTS: All children tolerated multiple doses of 129Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following 129Xe MRI, but all were deemed unrelated to the study. CONCLUSION: The feasibility, safety and tolerability of 129Xe MRI has been assessed in a small group of children as young as 6 years. SpO2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were consistent with the known anesthetic properties of xenon and with previous safety assessments of 129Xe MRI in adults. Hyperpolarized 129Xe is a safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in healthy children and in children with cystic fibrosis who have mild to moderate lung disease.