Insights into photoacoustic speckle and applications in tumor characterization

Abstract

In ultrasound imaging, fully-developed speckle arises from the spatiotemporal superposition of pressure waves backscattered by randomly distributed scatterers. Speckle appearance is affected by the imaging system characteristics (lateral and axial resolution) and the random-like nature of the underlying tissue structure. In this work, we examine speckle formation in acoustic-resolution photoacoustic (PA) imaging using simulations and experiments. Numerical and physical phantoms were constructed to demonstrate that PA speckle carries information related to unresolved absorber structure in a manner similar to ultrasound speckle and unresolved scattering structures. A fractal-based model of the tumor vasculature was used to study PA speckle from unresolved cylindrical vessels. We show that speckle characteristics and the frequency content of PA signals can be used to monitor changes in average vessel size, linked to tumor growth. Experimental validation on murine tumors demonstrates that PA speckle can be utilized to characterize the unresolved vasculature in acoustic-resolution photoacoustic imaging.

Photoacoustic simulations of microvascular bleeding: spectral analysis and its application for monitoring vascular-targeted treatments

“…Since the size of the vessels is smaller than the system resolution of 50 μm, it is difficult to extract image features that would suggest changes in the vascular structure. 13 Visual inspection of the B-mode images shows little difference in the images generated from the bleeding and nonbleeding vessels. The parameters of the vascular tree model are used to approximate the vascular geometry of real tissue vessels.…”

“…However, microvessels deep in tissue cannot be resolved using acoustic-resolution PA imaging. Ultrasound frequency analysis of the PA signals has been shown to detect changes smaller than the system resolution, [11][12][13] and this analysis may permit assessment of microvessel bleeding. The ability to detect and quantify the occurrence of bleeding can have an important role for PA modeling in cancer therapy.…”

“…Changes in the frequency content of the PA signals are associated with the size, concentration, and spatial distribution of dominant optical absorbing chromophores. [13][14][15] This is analogous to quantitative ultrasound analysis, which is associated with the dominant ultrasound scattering source. 16,17 PA spectral analysis provides system-independent parameters that are correlated to the structure of optically absorbing chromophores.…”

“…The advantages of PA spectral analysis have been used in assessing tumors, liver conditions, and osteoporotic patients. 12,13,[19][20][21][22][23] For cancer monitoring, a decrease in the PA spectral slope at multiple wavelengths (45% at 750 nm and 73% at 850 nm) has been reported 2 h after introducing a VDA (HaT-DOX). 9 The changes in the spectral slope have been linked to hemorrhaging of blood vessels.…”

Experimental design and numerical investigation of a photoacoustic sensor for a low-power, continuous-wave, laser-based frequency-domain photoacoustic microscopy

“…20,21 Hence, OR-PAM has been used to image biological samples and small animals with various endogenous or exogenous contrasts 20 whereas AR-PAM finds both preclinical and clinical applications as deep imaging of biological tissues is possible at lower ultrasound frequencies. 22,23 Researchers are also interested in noncontact PA systems for remote sensing. Most of the noncontact PA systems are based on an interferometric principle.…”