Photoacoustic Mouse Brain Imaging Using an Optical Fabry-Pérot Interferometric Ultrasound Sensor

Abstract

Photoacoustic (PA, or optoacoustic, OA) mesoscopy is a powerful tool for mouse cerebral imaging, which offers high resolution three-dimensional (3D) images with optical absorption contrast inside the optically turbid brain. The image quality of a PA mesoscope relies on the ultrasonic transducer which detects the PA signals. An all-optical ultrasound sensor based on a Fabry-Pérot (FP) polymer cavity has the following advantages: broadband frequency response, wide angular coverage and small footprint. Here, we present 3D PA mesoscope for mouse brain imaging using such an optical sensor. A heating laser was used to stabilize the sensor's cavity length during the imaging process. To acquire data for a 3D angiogram of the mouse brain, the sensor was mounted on a translation stage and raster scanned. 3D images of the mouse brain vasculature were reconstructed which showed cerebrovascular structure up to a depth of 8 mm with high quality. Imaging segmentation and dual wavelength imaging were performed to demonstrate the potential of the system in preclinical brain research.

Keywords: Fabry-Pérot interferometer; brain imaging; mesoscopy; multiwavelength imaging; photoacoustic.

FIGURE 1

Imaging setup and sensor characterization: (A) schematic of the imaging system setup and the sensor structure. The mouse and the excitation beam were static during imaging while the sensor was raster-scanned by the XY stage. The fiber sensor was inserted into the hole of the glass base and fixed by UV-curing adhesive. (B) Frequency response at normal incidence obtained by Fast Fourier Transform (FFT) of the corresbonding temporal response shown in inset. The –3 dB bandwidth is measured using the dashed lines. (C) Frequency response of the FPI sensor under varying incident angle from –90 to 90°.

FIGURE 2

Resolution measurements: (A) image of nine 9 μm diameter tengsten wires. The resolution measurement process is illustrated with the bright spot inside the blue circle. The horizontal and vertical cross sections of the spot are shown in “×” and were fitted by Gaussian functions. The FWHM was then estimated. Red indicates lateral direction and green indicates axial direction. (B) Resolution as a function of imaging depth. The discrete points correspond to the bright spots in (A).

FIGURE 3

Imaging results: (A) imaging area (shown in orange) and position of the cranial window (shown in red). (B) MIP of the 3D imaing result from inclined top view. (C) MIP of the imaing result in x-y plane. (D) MIP in x-z plane. (E) MIP in y-z plane. (C–E) Are color coded along the z direction.

FIGURE 4

The segmentation result of the cerebovascular structure. (A) The same view with Figure 3B. (B) Left view. (C) Horizontal slice plane at lateral-medial of the brain, inferior view. (D) Bottom view, showing the circle of Willis. Sss, superior sagittal sinus; Trs, transverse sinises; Crhv, caudal rhinal vein; Gcv, vein of galen; sts, straight sinus; Lhiv, longitudinal hippocampal vein; Thsv, thalamostriate vein; Mcolv, medial collicular vein; Lcolv, lateral collicular vein; Ictd, internal carotid artery; Acer, anterior cerebral artery; Mcer, middle cerebral artery; Pcer, posterior cerebral artery; Ach, anterior choroidal artery; Azp, azygos pericallosal; Pcom, posterior communication artery; Scba, superior cerebellar artery.

FIGURE 5

Double wavelength imaging results. (A) Averaged PAA of different vessels. Arteries has larger PAA at 1,064 nm and veins has larger PAA at 800 nm. (B) MIP of the sum of the PA images excited at 1,064 and 800 nm in the x-y plane. (C) MIP in the x-z plane. (D) MIP in the y-z plane. (B–D) Are color coded by the difference of the two PA images excited at 1,064 and 800 nm.