Multiscale photoacoustic microscopy and computed tomography

Abstract

Photoacoustic tomography (PAT) is probably the fastest growing biomedical imaging technology owing to its capability of high-resolution sensing of rich optical contrast in vivo at depths beyond the optical transport mean free path (~1 mm in the skin). Existing high-resolution optical imaging technologies, such as confocal microscopy and two-photon microscopy, have fundamentally impacted biomedicine but cannot reach such depths. Taking advantage of low ultrasonic scattering, PAT indirectly improves tissue transparency by 100 to 1000 fold and consequently enables deeply penetrating functional and molecular imaging at high spatial resolution. Further, PAT holds the promise of in vivo imaging at multiple length scales ranging from subcellular organelles to organs with the same contrast origin, an important application in multiscale systems biology research.

Figure 1. Multiscale scanning photoacoustic imaging of small animals in vivo

(a) Annotated photograph of the dark-field confocal photoacoustic microscope. (b) Photoacoustic image of a melanoma and blood vessels acquired with a 50-MHz photoacoustic microscope. M: melanoma. Axial resolution: 15 μm. Penetration limit: 3 mm. (c) Photoacoustic image of a sentinel lymph node (SLN) 18 mm below the laser-illumination surface acquired with a 5-MHz photoacoustic macroscope. Axial resolution: 144 μm. Penetration limit: 30 mm. (d) Photoacoustic image of the vasculature, including capillaries, acquired with an optical-resolution photoacoustic microscope. Lateral resolution: 5 μm. Penetration limit: 0.7 mm.

Figure 2. Non-invasive photoacoustic computed tomography of small animals

(a) Functional images of a rat brain acquired in vivo with left- and right-side whisker stimulations, respectively. Color: differential absorption ΔA_e due to brain activation. Gray: structure of the cortex. Field of view: 20 × 20 mm. (b) Left: Schematic of superficial cerebral vascular anatomy: A, superior sagittal sinus; B, lateral sinus; C, inferior cerebral vein. Right: Image of a mouse brain acquired ex vivo with a system based on Fabry-Perot interferometry. (c) Whole-body image of a mouse acquired in vivo, where a 10-mm thick section of the abdomen is shown.

Figure 3. In vivo photoacoustic computed tomography of the human breast acquired at 1064-nm laser wavelength

(a) Image of a human breast containing a poorly differentiated infiltrating ductal carcinoma. The slice is 21 mm deep from the laser-illumination surface. Field of view: 120 × 120 mm. (b) Image of a breast containing an invasive ductal carcinoma. The slice is 13.5 mm deep from the laser-illumination surface.