Quantifying Diaphragm Blood Flow With Contrast-Enhanced Ultrasound in Humans
Jordan D. Bird, Megan L. Lance, Ty R W Banser, Scott F. Thrall, Paul D. Cotton, Jonathan R. Lindner, Neil D. Eves, Paolo B. Dominelli, Glen E. Foster
Abstract
Background Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow ( Q ˙ DIA ) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q ˙ DIA would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility. Research Question Can we validate what is, to our knowledge, the first minimally invasive method to measure relative diaphragm blood flow in humans? Study Design and Methods Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male participants, 6 female participants; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured transdiaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q ˙ DIA by two individuals. Results Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q ˙ DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 acoustic units/s; P < .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q ˙ DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P < .0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P < .0001) with minimal bias. Interpretation Relative Q ˙ DIA measurements had valid physiological underpinnings, were reliable day-to-day, and were reproducible analyzer-to-analyzer. This study indicated that contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q ˙ DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.