Multiscale investigations of spatially heterogeneous alveolar stress
EMSL Project ID
48202
Abstract
Multiscale investigations of spatially heterogeneous alveolar stress: The focus of this work is the co-location of mass spectrometry imaging (MSI) signals of inflammation biomarkers with kinematic data from dynamic ?-CT data in the context of ventilator induced lung injury (VILI). In brief, mechanical ventilation is currently the only effective treatment of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). However, mechanical ventilation can result in additional injury. The mechanisms of VILI are related to altered and extreme stresses in the micromechanical environment of the alveoli. Despite decades of research mortality rates for patients with ARDS/ALI remains unacceptably high at 40-60%. We are developing a modeling framework that will enable a clinician to pre-screen patients in terms of their vulnerability to specific ventilation protocols by predicting local alveolar scale stress. Stress however is not measurable and thus no direct data exists to validate our modeling assumptions. Extreme alveolar scale stresses do, however, produce well-characterized and well-understood inflammatory pathways. Thus, in this work we will measure and compute local ventilation from ?-CT data from control and VILI animals and correlate it with MSI data from the same animals such that differences in the spectra between the two groups can be used to reveal spatial patterns of inflammation. The scope of this work is limited. For example, stresses will not be predicted in the modeling framework we are developing. Rather the intent is to produce compelling preliminary data for the resubmission of our NIH-UO1 proposal Multiscale investigation of spatially heterogeneous alveolar stresses in ventilator-induced lung injury – in response to PAR-11-203. Specifically, we propose 1) to develop, test and analyze ?-CT data from a set of control and VILI Sprague-Dawley rats; and 2) to acquire a set of MSI data to identify hallmarks of VILI with MALDI-FT-ICR MS to be performed on sections from the same rats imaged in 1). The VILI rats will be exposed to a high-tidal volume ventilation protocol that has been shown to produce VILI in rodents, but with which we have no prior experience.
Project Details
Start Date
2013-11-26
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator