Ethyl pyruvate improves pulmonary function in mice with bleomycin-induced lung injury as monitored with hyperpolarized 129Xe MR imaging

Purpose: High Mobility Group Box1 (HMGB1), which is one of the damage-associated molecular pattern molecules relating to various inflammatory diseases, has gained interest as a therapeutic target because of its involvement in wound healing processes. In the present study, we investigated HMGB1 as a potential therapeutic target in a model of lung fibrosis using a preclinical hyperpolarized 129Xe (HPXe) MRI system. Methods: Lung injury was induced by intra-peritoneal injection of bleomycin (BLM) in 19 mice. Three weeks post-injection (when fibrosis was confirmed histologically), administration of ethyl pyruvate (EP) and alogliptin (ALG), which are down- and up-regulators of HMGB1, respectively, was commenced in six and seven of the 19 mice, respectively, and continued for a further 3 weeks. A separate sham-instilled group was formed of five mice, which were administered with saline for 6 weeks. Over the second 3-week period, the effects of disease progression and pharmacological therapy in the four groups of mice were monitored by HPXe MRI metrics of fractional ventilation and gas-exchange function. Results: Gas-exchange function in BLM mice was significantly reduced after 3 weeks of BLM challenge compared to sham-instilled mice (P < 0.05). Ethyl pyruvate was found to improve HPXe MRI metrics of both ventilation and gas exchange, and repair tissue damage (assessed histologically), to a similar level as sham-instilled mice (P < 0.05), whilst ALG treatment caused no significant improvement of pulmonary function. Conclusion: This study demonstrates the down-regulator of HMGB1, EP, as a potential therapeutic agent for pulmonary fibrosis, as assessed by a non-invasive HPXe MRI protocol

Simultaneous 3D acquisition of ¹ H MRF and ²³ Na MRI.

To develop a 3D MR technique to simultaneously acquire proton multiparametric maps (T &lt;sub&gt;1&lt;/sub&gt; , T &lt;sub&gt;2&lt;/sub&gt; , and proton density) and sodium density weighted images over the whole brain. We implemented a 3D stack-of-stars MR pulse sequence which consists of interleaved proton ( &lt;sup&gt;1&lt;/sup&gt; H) and sodium ( &lt;sup&gt;23&lt;/sup&gt; Na) excitations, tailored slice encoding gradients that can encode the same slice for both nuclei, and simultaneous readout with different radial trajectories ( &lt;sup&gt;1&lt;/sup&gt; H, full-radial; &lt;sup&gt;23&lt;/sup&gt; Na, center-out radial). The receive chain of our 7T scanner was modified to enable simultaneous acquisition of &lt;sup&gt;1&lt;/sup&gt; H and &lt;sup&gt;23&lt;/sup&gt; Na signal. A heuristically optimized flip angle train was implemented for proton MR fingerprinting (MRF). The SNR and the accuracy of proton T &lt;sub&gt;1&lt;/sub&gt; and T &lt;sub&gt;2&lt;/sub&gt; were evaluated in phantoms. Finally, in vivo application of the method was demonstrated in five healthy subjects. The SNR for the simultaneous measurement was almost identical to that for the single-nucleus measurements (&lt;2% change). The proton T &lt;sub&gt;1&lt;/sub&gt; and T &lt;sub&gt;2&lt;/sub&gt; maps remained similar to the results from a reference 2D MRF technique (normalized RMS error in T &lt;sub&gt;1&lt;/sub&gt; ≈ 4.2% and T &lt;sub&gt;2&lt;/sub&gt; ≈ 11.3%). Measurements in healthy subjects corroborated these results and demonstrated the feasibility of our method for in vivo application. The in vivo T &lt;sub&gt;1&lt;/sub&gt; values measured using our method were lower than the results measured by other conventional techniques. With the 3D simultaneous implementation, we were able to acquire sodium and proton density weighted images in addition to proton T &lt;sub&gt;1&lt;/sub&gt; , T &lt;sub&gt;2&lt;/sub&gt; , and from &lt;sup&gt;1&lt;/sup&gt; H MRF that covers the whole brain volume within 21 min