In vivo imaging of the progression of acute lung injury using hyperpolarized [1‐¹³C] pyruvate

Abstract

Purpose To investigate pulmonary metabolic alterations during progression of acute lung injury. Methods Using hyperpolarized [1-13C] pyruvate imaging, we measured pulmonary lactate and pyruvate in fifteen ventilated rats one, two and four hours after initiation of mechanical ventilation. Lung compliance was used as a marker for injury progression. Five untreated rats were used as controls; five rats (injured-1) received 1 ml/kg and another five rats (injured-2) received 2 ml/kg hydrochloric acid (pH 1.25) in the trachea at 70 minutes. Results The mean lactate-to-pyruvate ratio of the injured-1 cohort was 0.15±0.02 and 0.15±0.03 at baseline and one hour after the injury, and significantly increased from the baseline value three hours after the injury to 0.23±0.02 (p=0.002). The mean lactate-to-pyruvate ratio of the injured-2 cohort decreased from 0.14±0.03 at baseline to 0.08±0.02 one hour after the injury and further decreased to 0.07±0.02 (p=0.08) three hours after injury. No significant change was observed in the control group. Compliance in both injured groups decreased significantly after the injury (p<0.01). Conclusion Our findings suggest that in severe cases of lung injury, edema and hyperperfusion in the injured lung tissue may complicate interpretation of the pulmonary lactate-to-pyruvate ratio as a marker of inflammation. However, combining the lactate-to-pyruvate ratio with pulmonary compliance provides more insight into the progression of the injury and its severity.

Optimisation of pyruvate hyperpolarisation using SABRE by tuning the active magnetisation transfer catalyst

“…[4][5][6] Rapid heating of such solids then generates materials that yield MR signal enhancements in solution of up to 5 orders of magnitude. 5,6 This approach has been applied to the production of hyperpolarised biomolecules such as pyruvate, [7][8][9][10][11][12][13][14] succinate, 15,16 and fumarate 17,18 which are then injected and detected in vivo alongside their metabolic byproducts. Imaging the formation of such metabolites provides a route to studying biochemical tissue function in real time with obvious benefits for disease diagnosis.…”

“…Imaging the formation of such metabolites provides a route to studying biochemical tissue function in real time with obvious benefits for disease diagnosis. [7][8][9][10][11][12][13][14][15][16][17] Para-Hydrogen induced polarisation (PHIP) methods are potentially a faster and cheaper alternative to DNP. [19][20][21] The feedstock of PHIP is para-hydrogen (p-H 2 ), which is the isomer of dihydrogen that exists as a nuclear spin singlet.…”

Metabolic Imaging and Biological Assessment: Platforms to Evaluate Acute Lung Injury and Inflammation

“…Treatment either results in resolution of ARDS/ALI or in the syndrome’s progression into severe respiratory failure, pulmonary fibrosis and eventual multi-organ failure. Reproduced with permission from Pourfathi (2019) .…”

“…(C) Area under each peak depicted as a function of time to represent the relative concentration of each peak. Reproduced with permission from Pourfathi (2019) .…”

Detection of lung transplant rejection in a rat model using hyperpolarized [1‐13C] pyruvate‐based metabolic imaging

“…Hyperpolarized (HP) [1‐ 13 C] pyruvate MRI is a novel imaging technique that provides such a real‐time metabolic assessment of tissue; the signal of an injected carbon‐13‐enriched molecular probe can be enhanced more than 10 000‐fold compared with thermal polarization via dynamic nuclear polarization (DNP), allowing molecular pathways to be imaged within minutes . The lactate‐to‐pyruvate ratio (LtP) derived from this technique has been used in rat models of lung injury as a biomarker for ischemia reperfusion, acute injury and inflammation . Given the central role that these mechanisms play in lung tissue rejection, HP [1‐ 13 C] pyruvate MRI appears to hold significant promise as a biomarker for the early detection of lung rejection.…”