title: Ultrasound-based measurement of molecular marker concentration in large blood vessels: a feasibility study.
abstract: Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols because of waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated acoustic radiation force-based imaging sequence, which was found to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine its feasibility for quantitative measurements of molecular marker concentration. Results indicated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p > 0.13, n = 10) when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R(2) > 0.94). Consequently, feasibility was illustrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated acoustic radiation force-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols (3 min) without control measurements.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Shiying
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: F William
authors.initials: FW
authors.lastname: Mauldin
authors.affiliation: Division of Cardiovascular Medicine and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.affiliation: Department of Biomedical Engineering and Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia, USA. Electronic address: jh7fj@virginia.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Hossack
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001808:Blood Vessels / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D057054:Molecular Imaging / Q000379:methods*; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Acoustic radiation force; Molecular imaging; Quantitative measurement; Ultrasound