Introduction

Chest radiography and computed tomography (CT) are used to monitor the progression or resolution of acute lung injury. While powerful, these techniques only reveal structural and morphological changes in the tissue, which may supersede otherwise undetectable functional and cellular changes. Recent advancements in hyperpolarized (HP) MRI technologies have enabled new approaches to probe regional structural and functional parameters in the lungs using ¹²⁹Xe MRI and lung tissue metabolism using [1-¹³C] pyruvate MRI^1,2. Here, we sought to demonstrate the combined use of these technologies to assess lung injury in pig model of aspiration pneumonitis, using a setup similar to what would be used clinically. Our data shows the potential for an such integrated imaging approach to comprehensively assess lung injury.

Materials and Methods

Two Yorkshire pigs were ventilated (V_T=10 ml/kg, PEEP=0-5 cmH₂O, F_iO₂=0.5-1, f=15 min^-1) in supine position. Hydrochloric acid (HCl, pH 1.0) was delivered to the base of the lungs using a bronchoscope, after which animals remained on the ventilator. Animals’ temperature was kept between 36.5-38.5°C during the study using a blanket that circulates heated water. 7 hours after acid instillation, ¹²⁹Xe imaging was performed using a 1.5T Siemens Avanto clinical MRI system. ¹²⁹Xe signal was acquired using an 8-channel ¹²⁹Xe flex-coil. 2L of enriched 129Xe gas was polarized using a XeBox-E10 commercial prototype polarizer (Xemed, LLC, Durham, NH). A mixture of 20% oxygen and 80% HP ¹²⁹Xe was delivered to the pigs using a custom-made ventilator. Two-dimensional projection gas and dissolved phase axial images were simultaneously obtained using an RF-spoiled GRE sequence (in-plane FOV = 20x57 cm², matrix-size = 28x80, TR/TE = 30/2.4 ms, flip-angle (dissolved/gas) = 20^o/1^o with a 900 ms Gaussian pulse centered on the dissolved phase peak)3. After a 1-hour ¹²⁹Xe imaging session, animals were transported to a 3T Siemens Trio clinical MRI system for 13C imaging; ¹³C images were obtained using an 8-channel ¹³C flex-coil. Samples containing 640 mg of [1-¹³C] pyruvate mixed with 15mM of AH111501 EPA were polarized using a 5T SpinLab DNP hyperpolarizer. 1ml/kg of 250 mM neutralized isotonic HP [1-¹³C] pyruvate sample was injected through the ear vein over 30 seconds, and chemical shift imaging was started using a modified FID-CSI sequenced 40 seconds after the start of injection (in-plane FOV=20x20 mm², slice-thickness=5 cm, matrix-size=16x16, flip-angle=6^o, spectral-width=2,560 Hz, TR=52 ms). A 15 second breath-hold was applied to minimize imaging artifacts due to respiratory motion. Localizers and T2-weighted anatomical images were obtained prior to each HP study.

Results and Discussion

Representative HP ¹²⁹Xe gas and dissolved phase maps as well as HP [1-¹³C] pyruvate and [1-¹³C] lactate maps overlaid on the corresponding anatomical T₂ image are shown below. Lactate signal is elevated in the posterior region of both lungs; however, the ¹²⁹Xe scan shows low ventilation and gas uptake only in the right lung (white arrow). We previously showed that HP ¹³C MRI is capable of detecting regions with elevated lactate production in the lungs due to injury in-vivo². Although our findings suggested that elevated lactate-to-pyruvate ratio is strongly associated with early inflammatory activity, it is not unambiguously identifiable as a precursor to lung injury progression since it may also result from hypoxia, ischemia or atelectrauma. Using HP ¹²⁹Xe MRI, we can identify injury-induced structural and functional alterations by obtaining local measurements of oxygen tension, specific ventilation and gas uptake^3,4. This additional information can potentially improve the specificity of our ¹³C HP-MRI: e.g., by co-localizing the alveolar oxygen tension map attained with HP ¹²⁹Xe MRI and the lactate-to-pyruvate map measured via ¹³C HP-MRI, allowing us to sensitively distinguish between hypoxia and inflammatory response.

Conclusions

In this study, we demonstrated the feasibility of using HP ¹³C and ¹²⁹Xe imaging as a multi-modality approach to characterize lung injury. While ¹³C MRI highlights regions with abnormal metabolism, ¹²⁹Xe MRI can provide additional information regarding gas uptake and ventilation, thereby enabling a more comprehensive characterization of the injured lung. This can ultimately lead to better patient outcomes by enabling both earlier injury detection and earlier selection of the appropriate management strategy to resolve the injury.

Acknowledgements

This work was supported by NIH (Bethesda, MD, USA) grants R01-HL124986 and R01-HL139066.