Prospects of photoacoustic tomography

Abstract

Commercially available high-resolution three-dimensional optical imaging modalities-including confocal microscopy, two-photon microscopy, and optical coherence tomography-have fundamentally impacted biomedicine. Unfortunately, such tools cannot penetrate biological tissue deeper than the optical transport mean free path (approximately 1 mm in the skin). Photoacoustic tomography, which combines strong optical contrast and high ultrasonic resolution in a single modality, has broken through this fundamental depth limitation and achieved superdepth high-resolution optical imaging. In parallel, radio frequency-or microwave-induced thermoacoustic tomography is being actively developed to combine radio frequency or microwave contrast with ultrasonic resolution. In this Vision 20/20 article, the prospects of photoacoustic tomography are envisaged in the following aspects: (1) photoacoustic microscopy of optical absorption emerging as a mainstream technology, (2) melanoma detection using photoacoustic microscopy, (3) photoacoustic endoscopy, (4) simultaneous functional and molecular photoacoustic tomography, (5) photoacoustic tomography of gene expression, (6) Doppler photoacoustic tomography for flow measurement, (7) photoacoustic tomography of metabolic rate of oxygen, (8) photoacoustic mapping of sentinel lymph nodes, (9) multiscale photoacoustic imaging in vivo with common signal origins, (10) simultaneous photoacoustic and thermoacoustic tomography of the breast, (11) photoacoustic and thermoacoustic tomography of the brain, and (12) low-background thermoacoustic molecular imaging.

Figures

Figure 1

(a) Photograph of a melanoma in a nude mouse; (b) image acquired with the 50-MHz photoacoustic microscope operating at 584 and 764 nm. Composite of the two maximum amplitude projection (MAP) images projected along the z axis. Six orders of vessel branching (1–6) can be observed. (c) 3D rendering of the melanoma image acquired at 764 nm. Two MAP images at this wavelength projected along the x and y axes are shown on the sidewalls. The composite image in panel b is redrawn at the bottom. The top of the tumor is 0.32 mm below the skin surface, and the thickness of the tumor is 0.3 mm. (d) Close-up two-dimensional image of the melanoma in a cross-section parallel with the z-x plane at the dashed line in panel b. (e) HE-stained histological section at the same marked location. M: melanoma. Reproduced with permission (Fig. 2 of Ref. 34).

Figure 2

(a) In vivo functional PAT image of hemoglobin in a nude mouse brain with a U87 glioblastoma xenograft. The arrow indicates the hypoxic region. (b) In vivo molecular PAT image of tail-vein injected IRDye800-c(KRGDf) in the same nude mouse brain. The circle indicates the region of integrin overexpression. Reproduced with permission (Figs. 2 and 3 of Ref. 31).

Figure 3

(a) Image acquired with the 5-MHz photoacoustic imaging system showing the 30 mm penetration limit in chicken breast tissue. Reproduced with permission (Fig. 2) (Ref. 51). (b) Photograph taken with transmission optical microscopy showing the microvasculature in a nude mouse ear. (c) In vivo photoacoustic image of the vasculature acquired with optical-resolution photoacoustic microscopy. CL: capillary; SG: sebaceous gland. Reproduced with permission (Fig. 3 of Ref. 52).