Photoacoustic imaging and characterization of the microvasculature

Abstract

Photoacoustic (optoacoustic) tomography, combining optical absorption contrast and highly scalable spatial resolution (from micrometer optical resolution to millimeter acoustic resolution), has broken through the fundamental penetration limit of optical ballistic imaging modalities-including confocal microscopy, two-photon microscopy, and optical coherence tomography-and has achieved high spatial resolution at depths down to the diffusive regime. Optical absorption contrast is highly desirable for microvascular imaging and characterization because of the presence of endogenous strongly light-absorbing hemoglobin. We focus on the current state of microvascular imaging and characterization based on photoacoustics. We first review the three major embodiments of photoacoustic tomography: microscopy, computed tomography, and endoscopy. We then discuss the methods used to characterize important functional parameters, such as total hemoglobin concentration, hemoglobin oxygen saturation, and blood flow. Next, we highlight a few representative applications in microvascular-related physiological and pathophysiological research, including hemodynamic monitoring, chronic imaging, tumor-vascular interaction, and neurovascular coupling. Finally, several potential technical advances toward clinical applications are suggested, and a few technical challenges in contrast enhancement and fluence compensation are summarized.

Figure 1

Schematic of the OR-PAM system. Reproduced with permission from Ref. .

Figure 2

Representative microvascular network in a nude mouse ear imaged in vivo by OR-PAM: (a) maximum amplitude projection image and (b) 3-D morphology. Reproduced with permission from Ref. .

Figure 3

Schematic of the dark-field AR-PAM system. Reproduced with permission from Ref. .

Figure 4

Structural imaging of the subcutaneous microvasculature in a rat in vivo: (a) maximum amplitude projection image and (b) 3-D morphology. Reproduced with permission from Ref. .

Figure 5

Schematic of the 48-element linear-array-based PACT system. Reproduced with permission from Ref. . PCI: peripheral component interconnect; DAQ: data acquistion; LDPF: low-density polyethylene.

Figure 6

Schematic of the 512-element ring-array-based PACT system. Reproduced with permission from Ref. . MSPS: mega samples/s; MUX: multiplexer; FPGA: field-programmable gate array.

Figure 7

Schematic of the FPI-based PACT system. Reproduced with permission from Ref. . OPO: optical parametric oscillator; DSO: digitizing oscilloscope.

Figure 8

FPI-based PACT of the vasculature in a human palm in vivo. Excitation wavelength is 670 nm. Left, photograph of the imaged region; middle, volume rendered image; and right, lateral slices at different depths. The arrow A indicates the deepest visible vessel, which is located 4 mm beneath the surface of the skin. Reproduced with permission from Ref. .

Figure 9

Schematic of the B-mode PAE system. Reproduced with permission from Ref. .

Figure 10

(a) Photograph of a PAE-inserted intestinal tract. The yellow dotted arrow indicates the scanning direction. Photoacoustic images are represented in (b) Cartesian coordinates and (c) polar coordinates. The ROI is marked by white dotted circles in (a) and (b), and by a white block arrow in (c). Reproduced with permission from Ref. . (Color online only.)

Figure 11

Schematic for the photoacoustic Doppler flowmetry system. Reproduced with permission from Ref. .

Figure 12

Structural and functional microvascular imaging of a nude mouse ear in vivo by OR-PAM: (a) structural image acquired at 570 nm and (b) vessel-by-vessel sO₂ mapping based on dual-wavelength (570 and 578 nm) measurements. The calculated sO₂ values are shown in the color bar. PA, photoacoustic signal amplitude; A1, a representative arteriole; V1, a representative venule; yellow dashed line: the B-scan position for Fig. 13. Reproduced with permission from Ref. . (Color online only.)

Figure 13

Vasomotion and vasodilation in response to switching the physiological state between systemic hyperoxia and hypoxia: (a) B-scan monitoring of the changes in the cross section of arteriole A1 (movie available in the reference). (b) B-scan monitoring of the changes in the cross section of venule V1, (c) changes in arteriolar and venular diameters in response to changes in physiological state (raw data were smoothed via 60-point moving averaging to isolate the effect of vasodilation), (d) power spectrum of the arteriolar vasomotion tone, and (e) power spectrum of the venular vasomotion tone. Reproduced with permission from Ref. .

Figure 14

In vivo monitoring of the healing process of a laser-induced microvascular lesion by optical-resolution photoacoustic microscopy: (a) before laser destruction, (b) immediately after laser destruction, and (c) on each of the subsequent 12 days. The left image in each part, (a) through (c-12) is a photograph taken by a commercial transmission-mode optical microscope; the middle one is the front view of the 3-D microvascular morphology acquired by an optical-resolution photoacoustic microscope at 570 nm; the right one is the maximum-amplitude projection image overlaid by the sO₂ mapping of the laser-damaged region. Reproduced with permission from Ref. .

Figure 15

Spectroscopic photoacoustic tomography of a nude mouse brain with a U87 glioblastoma xenograft in vivo: (a) composite of segmented molecular image of IRDye800-c(KRGDf) and structural image and (b) sO₂ mapping. Reproduced with permission from Ref. .

Figure 16

Maximum-amplitude projection images of a microvascular network in a rat acquired in vivo by AR-PAM at the isosbestic optical wavelength of 584 nm (A) before, (B) 2 days after, and (C) 5 days after subcutaneous inoculation with BR7C5 tumor cells. Reproduced with permission from Ref. .