Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine - Critical Care Research
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Research Overview

Critical Care Research

Pain and Neurosciences Research

Biomedical Innovation

Ethics and Health Policy

Clinical Research

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Guido Musch Laboratory

Summary Science Features

COLLABORATIONS

Dr. Guido Musch's research is part of a broader collaborative research effort that involves other members of the Department of Anesthesia, Critical Care and Pain Medicine and of other Departments at Massachusetts General Hospital.

Jose G. Venegas, Ph.D., is the director of the Applied Biofluids Laboratory and has developed and implemented the 13N2-saline PET imaging technique used to non-invasively measure regional lung perfusion, shunt, and ventilation used in these studies.

Marcos F. Vidal Melo, M.D. Ph.D., has developed quantitative analytical methods to derive parameters of regional lung function and gas exchange from 13N2 kinetics and of neutrophil metabolic activity from [18F]FDG pulmonary uptake kinetics.

Tilo Winkler, Ph.D., has developed mathematical models of airway behavior.

R. Scott Harris, M.D., from the Pulmonary and Critical Care Unit, has performed studies on the redistribution of pulmonary perfusion in response to bronchoconstriction.

Beyond this core of researchers, we collaborate with investigators of the Departments of Radiology and Medicine at Massachusetts General Hospital, of Boston University's Department of Bioengineering and of Massachusetts Institute of Technology.

Researchers

RESEARCH TECHNIQUES

The main technique employed in these studies is PET imaging of 13N2 and [18F]FDG kinetics. In the 13N2-saline bolus infusion technique, developed by Dr. Venegas (Mijailovich et al. J Appl Physiol 1997;82:1154-1162; Galletti and Venegas J Appl Physiol 2002;93:1104-1114), regional perfusion and shunt are measured from the pulmonary kinetics of a bolus of 13N2 dissolved in saline solution and infused intravenously during a brief apnea. In the [18F]FDG technique, neutrophil metabolic activity is measured from the uptake rate of [18F]FDG (Musch et al. Anesthesiology 2007;106:723-735; Schroeder et al. J Nucl Med 2007;48:1889-1896; Schroeder et al. Acad Radiol 2008;15:763-775).

Figure 1

13N2 pulmonary kinetics and PET images at lower (upper panel) and higher (lower panel) PEEP. For the tracer kinetics, the imaged lung field was divided in 6 horizontal regions of interest (ROIs) of equal height, with ROI 1 being the least dependent and ROI 6 the most dependent ROI. Each symbol shape corresponds to the same ROI at lower (filled symbols) and higher (open symbols) PEEP. Images of one cross-sectional slice of lung are shown for illustration. A bolus of 13N2 in saline solution was infused intravenously over 3 seconds at the beginning of a 60-second apnea (left of vertical dotted line). The distribution of 13N2 during early apnea (between 5 and 10 seconds) reflects regional perfusion (Peak apnea image). The distribution of 13N2 at the end of apnea (between 40 and 60 seconds) is proportional to perfusion only to aerated alveolar units, which retain 13N2 during apnea (End-apnea image). A drop in tracer activity from a peak in early apnea to a plateau in late apnea reflects the presence of shunting units, which do not retain 13N2. Note that this drop became progressively greater from ROI 4 to ROI 6, reflecting the progressive increase of regional shunt fraction along dependent ROIs. The PEEP increment reduced the magnitude of the drop in tracer activity from peak to plateau in ROIs 4 through 6, reflecting the reduction of shunt fraction in dependent ROIs. The reduction of regional shunt can be visually appreciated from the images: Whereas at lower PEEP there was a substantial drop of tracer activity between peak and end-apnea images in the dorsal lung (arrowheads), this drop was considerably smaller at higher PEEP, indicating that aeration and gas exchange had been partly restored by the PEEP increment (from: Musch et al. Am J Respir Crit Care Med 2008;177:292-300).

Figure 2

Parametric images of [18F]FDG uptake rate after unilateral ventilator-induced lung injury (VILI). Only the lung on the right-hand side of the image was exposed to VILI. Note increased [18F]FDG uptake in the VILI-exposed lung compared to the contralateral control lung (upper image). When PEEP was applied to protect from VILI, [18F]FDG uptake was decreased, but remained higher than in the control lung (lower image). Adapted from Musch et al. Anesthesiology 2007;106:723-735.



 
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