Photoacoustic tomography: in vivo imaging from organelles to organs

Abstract

Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects.

Fig. 1

Major embodiments of PAT, with representative in vivo images. (A) OR-PAM of sO₂ in a mouse ear. (B) AR-PAM of normalized total hemoglobin concentration, [Hemoglobin], in a human palm. (C) Linear-array PACT of normalized methylene blue concentration, [Dye], in a rat sentinel lymph node (SLN). (D) Circular-array PACT of cerebral hemodynamic changes, Δ[Hemoglobin], in response to one-sided whisker stimulation in a rat. (E) PAE of a rabbit esophagus and adjacent internal organs, including the trachea and lung. UST: ultrasonic transducer.

Fig. 2

Multiscale PAT of organelles, cells, tissues, and organs in vivo. (A) Sub-wavelength (SW) PAM of melanosomes in the ear of a black mouse. (B) OR-PAM of individual red blood cells traveling along a capillary in a mouse ear. (C) AR-PAM of a nevus on a human forearm. (D) PACT of a human breast. (E) Imaging depth versus spatial resolution in PAT. SM, sub-micron; LA, linear-array.

Fig. 3

Multi-contrast PAT of tissue anatomy, function, molecular biomarkers, and gene expression. (A) OR-PAM of epithelial cell nuclei in the intestinal villi of a mouse ex vivo by excitation of DNA and RNA. (B) AR-PAM of a subcutaneously inoculated B16-melanoma and the surrounding vasculature on the back of a living mouse. (C) AR-PAM of a subcutaneously inoculated B16-melanoma labeled with targeted gold nanocages on the back of a living mouse. (D) Dual-contrast ultrasound (gray) and photoacoustic (green) imaging of a single-walled carbon nanotube targeted tumor in a living mouse. (E) Magnetomotive PAT of a polyvinyl alcohol phantom with three 2-mm-diameter inclusions. The left inclusion contains gold nanorods with absorption comparable to the 3 nM magnetic-gold hybrid nanoparticles placed in the center inclusion, and the right inclusion contains 3 nM magnetic nanoparticles. (F) AR-PAM of a lacZ-marked 9L gliosarcoma and the surrounding vasculature under the scalp of a living rat. (G) PACT of the brain of a six-month-old mCherry-expressing transgenic zebrafish. (H) OR-PAM of blood flow velocity and direction in the ear of a living mouse.