Photoacoustic imaging of cells in a three-dimensional microenvironment

Abstract

Imaging live cells in a three-dimensional (3D) culture system yields more accurate information and spatial visualization of the interplay of cells and the surrounding matrix components compared to using a twodimensional (2D) cell culture system. However, the thickness of 3D cultures results in a high degree of scattering that makes it difficult for the light to penetrate deeply to allow clear optical imaging. Photoacoustic (PA) imaging is a powerful imaging modality that relies on a PA effect generated when light is absorbed by exogenous contrast agents or endogenous molecules in a medium. It combines a high optical contrast with a high acoustic spatiotemporal resolution, allowing the noninvasive visualization of 3D cellular scaffolds at considerable depths with a high resolution and no image distortion. Moreover, advances in targeted contrast agents have also made PA imaging capable of molecular and cellular characterization for use in preclinical personalized diagnostics or PA imaging-guided therapeutics. Here we review the applications and challenges of PA imaging in a 3D cellular microenvironment. Potential future developments of PA imaging in preclinical applications are also discussed.

Nondestructive testing of native and tissue-engineered medical products: adding numbers to pictures

“…Optoacoustic or photoacoustic imaging (PAI) provides structural information that has been used in clinical applications (Figure 2C). It achieves high-resolution imaging in deep biological tissues by combining high optical contrast and high ultrasound resolution in a single modality with micrometer-scale resolution and millimeter-scale imaging depth [48,49]. In PAI, a nanosecond pulsed laser is used to stimulate the biological sample wherein molecules absorb light energy [24].…”

Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time

“…Higher frequencies are required to improve wavelength-determined resolutions. While imaging is possible at depths up to several centimeters, cellular resolution is not attainable at depths beyond ~3mm (Liu and Li, 2020).…”

Exogenous Contrast Agents in Photoacoustic Imaging: An In Vivo Review for Tumor Imaging

“…Due to the rising trend of imaging tumor tissues using PAI [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] (see Figure 2 ), this review summarizes the recent major developments in PAI. It summarizes the in vivo studies that utilize different contrast agents to produce an enhanced image.…”