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 due to 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 (ARF)-based imaging sequence, which was demonstrated to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine feasibility for quantitative measurements of molecular marker concentration. Results demonstrated 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 (R2> 0.94). Consequently, feasibility was demonstrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated ARF-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols(3 min) without control measurements.

Quantitative Ultrasound Molecular Imaging in Large Blood Vessel Environments

“…The results observed in the PDMS-based flow channels were in excellent agreement with the results obtained from tissue-mimicking gelatin phantoms in previous studies [64], [65], [166].…”

“…Although the control peak was observed consistently in previous studies under various acoustic and flow parameters, results were limited to in vitro experiments [64], [65]. Figure 5-11c, black arrow).…”

“…The modulated ARF imaging exhibited a reliable and rapid imaging protocol (3 min) in vivo [67], and the capability to quantify molecular marker concentration in vitro [65].…”

“…The details of this custom pulse sequence were described in previous studies [64], [65], [166]. Briefly, the sequence collected raw radiofrequency (RF) data continuously over 180 s at a frame …”

“…A parameter related to the normalized amount of residual adherent microbubbles was extracted from this sequence. In vitro studies have demonstrated several advantages of the modulated ARF approach, primarily including the ability to quantitatively measure molecular marker concentration along the large vessel wall [65], [166] using a short imaging sequence that does not require a separate control injection to normalize for non-specific binding [51], [63]. The ability to quantitatively measure the molecular marker concentration has potential clinical significance as it could enable better treatment for various therapies or interventional decisions such as by establishing more reliable and quantitative thresholds.…”