Contrast-enhanced ultrasound (CEUS) reveals perfusion of human bone fracture in acute-phase healing

Bone fractures are common injuries with reported non-union rates of up to 9%. Current treatments for non-union include surgery, which is expensive and involves significant morbidity. Microbubbles are used clinically in ultrasonography as contrast agents and have been shown to deliver therapeutics to desired locations by noninvasive stimulation of cavitation using extracorporeal ultrasound in preclinical studies. Contrast enhanced ultrasound (CEUS) has been used to determine the cause of established fracture non-unions, though this is not in widespread use clinically. This study aimed to test the hypothesis that peripherally injected microbubbles are detectable in acute fracture sites. Adult patients (18 – 75 yrs) with acute humeral shaft fractures were recruited to undergo CEUS within 28 days of injury. They underwent peripheral injection of SonoVue microbubbles with ultrasound imaging. B-mode and contrast-mode videos were collected and time-intensity curve analysis was used to assess for the presence of microbubbles at the fracture site. Ten patients were recruited, 8 underwent humeral shaft fracture scans with 7 analysed. All fracture sites demonstrated increased contrast signal following injection. The wash-in volume of microbubbles was greater than the wash-out volume in all cases, with a mean difference of 1.4 × 10⁻⁵ (± 1.7 × 10⁻⁵) (p=0.015 Wilcoxon Test). There was a noticeable decrease in PI and Time to Peak (TtP) with age of fracture, although this was not statistically significant (R² = 0.44, p = 0.1; R² = 0.24, p = 0.26, respectively). This study demonstrates that commercially available microbubbles perfuse acute fractures in ultrasonographically detectable quantities using commercially available equipment. John Wiley