Dynamic blood flow phantom with negative and positive photoacoustic contrasts.

Mustafa Sarimollaoglu,Hind J Jawad,Vladimir P Zharov,Alexandru S Biris

doi:10.1364/boe.9.004702

Abstract

In vivo photoacoustic (PA) flow cytometry (PAFC) has great clinical potential for early, noninvasive diagnosis of cancer, infections (e.g., malaria and bacteremia), sickle anemia, and cardiovascular disorders, including stroke prevention through detection of circulating white clots with negative PA contrast. For clinical applications, this diagnostic platform still requires optimization and calibration. We have already demonstrated that this need can be partially addressed by in vivo examination of large mouse blood vessels, which are similar to human vessels used. Here, we present an alternative method for PAFC optimization that utilizes novel, clinically relevant phantoms resembling pigmented skin, tissue, vessels, and flowing blood. This phantom consists of a scattering-absorbing medium with a melanin layer and plastic tube with flowing beads to model light-absorbing red blood cells (RBCs) and circulating tumor cells (CTCs), as well as transparent beads to model white blood cells and clots. Using a laser diode, we demonstrated the extraordinary ability of PAFC to dynamically detect fast-moving mimic CTCs with positive PA contrast and white clots with negative PA contrast in an RBC background. Time-resolved detection of the delayed PA signals from blood vessels demonstrated complete suppression of the PA background from the modeled pigmented skin. This novel, medically relevant, dynamic blood flow phantom can be used to calibrate and maintain PAFC parameters for routine clinical applications.

Highlights

Photoacoustic (PA) flow cytometry (PAFC) has shown major clinical promise for detecting rare circulating tumor cells (CTCs), bacteria, clots, and other abnormal cells in vivo [1,2,3]
Development of dynamic phantoms is complicated by the fact that, in real biotissue (Fig. 1(a)), laser irradiation of blood vessels generates continual PA background signals associated with strong absorption of hemoglobin (Hb) in many red blood cells (RBCs) in the detection volume
To address the need for a dynamic blood flow phantom strategically designed to meet the unique parameters of PAFC, we have developed a novel blood vessel and flow phantom to test PAFC in dynamic conditions

Summary

Introduction

Photoacoustic (PA) flow cytometry (PAFC) has shown major clinical promise for detecting rare circulating tumor cells (CTCs), bacteria, clots, and other abnormal cells in vivo [1,2,3]. We demonstrated that this need can be addressed through in vivo testing of relatively large mouse blood vessels (0.5–1 mm in diameter, such as jugular vein or aorta), which are similar in size, depth, and flow velocity to the blood vessels in the human hand [2]. This method is time-consuming and requires animal testing; a biomedically adequate, animal-free blood flow phantom that is fast, cost-effective, and well-suited for PAFC is still needed. For PA techniques, phantoms should have wellcharacterized, versatile, and stable thermal and acoustic parameters similar to those of biotissue [13,14,15,16]

Methods

Results

Discussion

Conclusion