Contrast agents for molecular photoacoustic imaging

Abstract

Photoacoustic imaging (PAI) is an emerging tool that bridges the traditional depth limits of ballistic optical imaging and the resolution limits of diffuse optical imaging. Using the acoustic waves generated in response to the absorption of pulsed laser light, it provides noninvasive images of absorbed optical energy density at depths of several centimeters with a resolution of ∼100 μm. This versatile and scalable imaging modality has now shown potential for molecular imaging, which enables visualization of biological processes with systemically introduced contrast agents. Understanding the relative merits of the vast range of contrast agents available, from small-molecule dyes to gold and carbon nanostructures to liposome encapsulations, is a considerable challenge. Here we critically review the physical, chemical and biochemical characteristics of the existing photoacoustic contrast agents, highlighting key applications and present challenges for molecular PAI.

Photoacoustic molecular rulers based on DNA nanostructures

“…Targeting this nanostructure to a specific biochemical process would enable highly efficient photoacoustic molecular imaging with translational potential. 32 In conclusion, we have shown that the process of fluorescence quenching can be exploited to create photoacoustic rulers, which could, in the future, be applied for studies of molecular interactions at depth in living subjects.…”

“…31 Here, we report a systematic study of PAT molecular rulers using DNA nanostructures to precisely tune the distance between a fluorophore and quencher pair suitable for in vivo imaging in the near-infrared (NIR) optical window. 32 We assess the absorbance, fluorescence and photoacoustic properties of our DNA nanostructures as a function of fluorophore-quencher separation distance. Importantly, we demonstrate experimentally the potential of PAT for performing nanoscale distance measurements at depth in tissue mimicking phantoms and also highlight the utility of DNA nanostructures to enhance the photoacoustic signal generation capabilities of small molecule fluorescent dyes.…”

Multiplexed imaging for diagnosis and therapy

“…PAI provides activatable molecular contrast, which can then be superimposed on an anatomical background provided by traditional US using macroscopic or microscopic imaging configurations 95 . Some endogenous biological molecules naturally exhibit sufficient photoacoustic conversion efficiency necessary for PAI contrast (in particular haemoglobin, for probing hypoxia 96 or angiogenesis 97 ), and likewise do exogenous fluorescent dyes used in traditional molecularly targeted OI strategies 98 . However, the customisable structure and composition of nanomaterials have motivated their status as perhaps the most 'engineerable' platforms for PAI, particularly for integrating photoacoustic imaging with MRI, OI and therapeutic strategies.…”

Ultrasound-guided spectral photoacoustic imaging of hemoglobin oxygenation during development

“…Photoacoustic imaging-using a short laser pulse to generate ultrasound transients from optical absorbers-improves image contrast while maintaining many advantages of ultrasound imaging. Introduction of targeted contrast agents for photoacoustic imaging provides information about molecular composition of in vivo tissues [13,14]. Imaging of function is a particular strength of photoacoustic techniquesmeasurements of hemoglobin oxygen saturation (sO 2 ) been demonstrated in phantoms [15] and preclinical models [16][17][18].…”