Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease.

Abstract

In patients with sickle cell disease (SCD), poor outcome measures compromise the potential success of clinical trials. Contrast-enhanced ultrasound (CEUS) is a technique that can non-invasively quantify deep tissue microvascular blood flow. We tested the hypothesis that CEUS of forearm skeletal muscle could be used to: 1) assess microvascular abnormalities that occur during vaso-occlusive crisis; and 2) test new therapies for SCD that are targeted to improving the status of the microcirculation. We performed a prospective study, CEUS perfusion imaging of resting forearm muscle was performed in adults with SCD: 1) during and after a pain episode, and 2) before, during, and after a 24-hour infusion of the investigative agent, regadenoson, an adenosine A2A agonist. CEUS destruction-replenishment time-intensity data were analyzed to measure microvascular blood flow, as well as its components, microvascular blood volume and flux rate. Serial CEUS measurements were obtained in 32 adults with SCD. For the studies during crisis, there was a 30% reduction in microvascular blood flow compared to steady-state (p = 0.031), a reduction that was largely due to microvascular flux rate. For the regadenoson group, a non-significant 25% increase in flux rate and 9% increase in microvascular blood flow compared to baseline were detected during infusion. In a study of adults with SCD, CEUS detected changes in microvascular blood flow associated with vaso-occlusive crises. No changes were found during an infusion of the adenosine A2A agonist, regadenoson. This study provides preliminary evidence that CEUS could detect blood flow changes consistent with SCD physiology.

• Authors: Jonathan R Lindner, Todd Belcik, Michael Widlansky, Leanne M Harmann, Matthew S Karafin, Nancy J Wandersee, Maneka Puligandla, Donna Neuberg, Joel Linden, Joshua J Field
• Journal: PloS one (PLoS One) Vol. 14 Issue 7 Pg. e0218783 ( 2019) ISSN: 1932-6203 [Electronic] United States
• PMID: 31276520 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A2 Receptor Agonists
• Contrast Media
• Purines
• Pyrazoles
• regadenoson

Topics

• Adenosine A2 Receptor Agonists (pharmacology)
• Adult
• Anemia, Sickle Cell (diagnostic imaging, physiopathology)
• Contrast Media
• Female
• Forearm (blood supply, diagnostic imaging, physiopathology)
• Humans
• Image Enhancement
• Male
• Microcirculation (drug effects, physiology)
• Middle Aged
• Muscle, Skeletal (blood supply, diagnostic imaging, physiopathology)
• Prospective Studies
• Purines (pharmacology)
• Pyrazoles (pharmacology)
• Regional Blood Flow (drug effects, physiology)
• Ultrasonography (methods)
• Young Adult