Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.
Until recently, molecular imaging using magnetic resonance (MR) has been limited by the modality’s low sensitivity, especially with non-proton nuclei. The advent of hyperpolarized (HP) MR overcomes this limitation by substantially enhancing the signal of certain biologically important probes through a process known as external nuclear polarization, enabling real-time assessment of tissue function and metabolism. The metabolic information obtained by HP MR imaging holds significant promise in the clinic, where it could play a critical role in disease diagnosis and therapeutic monitoring. This review will provide a comprehensive overview of the developments made in the field of hyperpolarized MR, including advancements in polarization techniques and delivery, probe development, pulse sequence optimization, characterization of healthy and diseased tissues, and the steps made towards clinical translation.
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.
Purpose To optimize the production of hyperpolarized 13C-bicarbonate from the decarboxylation of hyperpolarized [1-13C]pyruvate and use it to image pH in the lungs and heart of rats with acute lung injury. Methods Two forms of catalysis are compared calorimetrically to maximize the reaction rate of decarboxylation and rapidly produce hyperpolarized bicarbonate from pyruvate while minimizing signal loss. Rats are injured using an acute lung injury model combining VILI and acid aspiration. Carbon images are obtained from both healthy (n=4) and injured (n=4) rats using a slice-selective CSI sequence with low flip angle. pH is calculated from the relative HCO3− and CO2 signals using the Henderson-Hasselbalch equation. Results It is demonstrated that base-catalysis is more effective than metal-ion catalysis for this decarboxylation reaction. Bicarbonate polarizations up to 17.2% are achieved using the base-catalyzed reaction. A mean pH difference between lung and heart of 0.14 pH units is measured in the acute lung injury model. A significant pH difference between injured and uninjured lungs is also observed. Conclusions It is demonstrated that hyperpolarized 13C-bicarbonate can be efficiently produced from the base-catalyzed decarboxylation of pyruvate. This method is used to obtain the first regional pH image of the lungs and heart of an animal.
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