The Anesthesiologist as Translational Scientist.

Translational science seeks to accelerate the multi-step process by which scientific discoveries are transformed into therapies that can improve the health of individuals and their communities. To facilitate crossing the traditional boundaries between basic and clinical research for instance, a systematic understanding of the scientific and operational principles that underlie each step of the translational cycle is developed to identify and address barriers to translation. Skills required by translational scientists, such as being systems thinkers and process innovators, overlap with those of anesthesiologists, and therefore, it is no surprise that anesthesiologists have contributed to this field. Indeed, the safety and efficacy of anesthesia care has greatly evolved over many decades because anesthesiologists have recognized the importance of readily incorporating physiological and pharmacological basic research findings into clinical practice. This article highlights the characteristics that make anesthesiologists well suited to be translational scientists. We also discuss one example of anesthesiology contributing to the field of translational science during the COVID-19 pandemic. We show that anesthesiologists, regardless of their specific clinical or research interests, have the skill set to become effective and critical players in the field of translational science and emphasize the importance of continued leadership in this field to academic anesthesiology.

Multimodality molecular imaging of the alveolar-capillary barrier in lung disease using albumin based optical and PET tracers.

Inflammatory changes caused by viruses, bacteria, exposure to toxins, commonly used drugs and even surgical intervention have the potential of causing abnormal epithelial permeability, which is manifest as infiltrative processes on computed tomography (CT), including the widespread infiltrates seen in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). We utilized a previously published mouse model of ARDS, intranasal delivery of LPS, to induce the alveolar-capillary barrier permeability seen in lung disease. We intravenously injected mice with Cy7 or 68-Gallium (68Ga) labeled mouse albumin and imaged using optical imaging (OI)/CT and PET. We observed significantly increased lung levels of Cy7-albumin on 3D OI/CT, which matched the abnormal appearance on microCT. This uptake correlated with fluorescence seen on sectioned lungs. To examine the translational potential of these findings, we radiolabeled albumin with 68Ga. We found that in mice with LPS-induced lung injury, 68Ga-albumin PET correlated with our optical imaging findings and demonstrated abnormal activity in the lung fields, indicative of abnormal epithelial permeability. These findings indicate 68Ga-albumin can be utilized as a sensitive translational radiotracer for quantifying the abnormal epithelial permeability that is seen in various lung pathologies, including COVID-19 induced pneumonia and ARDS. The ability to use Cy7-albumin 3D OI/CT imaging as a preclinical translational surrogate for 68Ga-albumin offers an accessible high throughput means to rapidly screen potential therapeutics against lung diseases that clinically manifest with endothelial permeability.