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Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease. PLoS One 2019;14(7):e0218783



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Pubmed Central ID




Scopus ID

2-s2.0-85069268459   6 Citations


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.

Author List

Lindner JR, Belcik T, Widlansky M, Harmann LM, Karafin MS, Wandersee NJ, Puligandla M, Neuberg D, Linden J, Field JJ


Joshua J. Field MD Professor in the Medicine department at Medical College of Wisconsin
Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine A2 Receptor Agonists
Anemia, Sickle Cell
Contrast Media
Image Enhancement
Middle Aged
Muscle, Skeletal
Prospective Studies
Regional Blood Flow
Young Adult