Photoacoustic imaging as a highly efficient and precise imaging strategy for the evaluation of brain diseases

Abstract

Photoacoustic imaging (PAI) is an emerging imaging strategy with a unique combination of rich optical contrasts, high ultrasound spatial resolution, and deep penetration depth without ionizing radiation. Taking advantage of the features mentioned above, PAI has been widely applied to preclinical studies in diverse fields, such as vascular biology, cardiology, neurology, ophthalmology, dermatology, gastroenterology, and oncology. Among various biomedical applications, photoacoustic brain imaging has great importance due to the brain's complex anatomy and the variability of brain disease. In this review, we aimed to introduce a novel and effective imaging modality for diagnosing brain diseases. Firstly, a brief overview of two major types of PAI system was provided. Then, PAI's major preclinical applications in brain diseases were introduced, including early diagnosis of brain tumors, subtle changes in the chemotherapy response, epileptic activity and brain injury, foreign body, and brain plaque. Finally, a perspective of the remaining challenges of PAI was given for future advancements.

Keywords: Photoacoustic imaging; brain diseases; diagnosis; imaging modality.

Figure 1

Schematic diagram of the device. (A) Schematic representation of AR-PAM system, OR-PAM system, and their photoacoustic images (39); (B) Three categories: circular, spherical, and planar geometry transducers of the PACT imaging system and their photoacoustic images (40-43). AR-PAM, acoustic-resolution photoacoustic microscopy; OR-PAM, optical-resolution photoacoustic microscopy; PACT, photoacoustic computed tomography.

Figure 2

In vivo PAI of brain tumor. (A) PAI of tumor vessels prior to, 1 min after, and 48 h after laser irradiation. Red arrow denotes vascular tortuosity (56), Scale bar: 100 µm; (B) PAI of brain tumor region before, and after 24 h, of injection of nanoparticles showing blood vessels (gray) and brain tumor (green tumor) (57); (C) Representative PAI of brain tumor region before, and 12 h after, tail vein injection of contrast agents showing blood vessels (532 nm, red) and the nanoparticles accumulate in the brain tumor tissue (680 nm, green) (58); (D) In vivo PAI of tumor-bearing mice at a different time points after intravenous injection of nanoparticles (59). PAI, photoacoustic imaging.

Figure 3

Multi-modality photoacoustic imaging of brain tumors. US images (grey) and B-scan photoacoustic images (green) of the brain tumor before and after nanoparticles injection (60). US, ultrasound.

Figure 4

(A) Continuous monitoring imaging of the recovery process of photoacoustic brain injury (78); (B) Group averaged SO₂ weighted PAI for NaCl (controls) and LPS group (79); (C) Photoacoustic images of the mouse brain at predetermined time intervals of injury after 3 min, 1, 3, 5, 7, 9, 11, 13, and 15 days, respectively (80). PAI, photoacoustic imaging; LPS, lipopolysaccharide.

Figure 5

PAI of the tumor receiving chemotherapy by the conventional PACT system (A) and the PAM system (B), Scale bar =1 mm (90). The arrows indicated the tumor vasculature of the tumor receiving chemotherapy. PAI, photoacoustic imaging; PAM, photoacoustic microscopy; PACT, photoacoustic computed tomography.

Figure 6

Metal foreign body detection in the brain by PAI. (A) photoacoustic image acquired with two small copper wires inserted in the mouse brain; (B) X-ray images corresponding to (A); (C) Recombined image with both (A) and (B) (78). The copper wires are identified by the arrows. PAI, photoacoustic imaging.

Figure 7

PAI of brain plaque in mouse brain. (A) Photoacoustic maximum amplitude projection images recorded for Tg mice after an injection of contrast agents at different time points; the yellow arrows indicated the brain plaque in blood vessels of mouse. (B) Photoacoustic signal enhancement in mice brains of Tg (101). PAI, photoacoustic imaging; Tg, transgenic.

Figure 8

MSOT images for the brains of three MCAO mice (left to right) with corresponding HE stained cryosections for each mouse (bottom; per mouse). From top down: Pre-, during, and 24 h post-ischemia. Data for deoxygenated hemoglobin are presented in blue (108). MSOT, multispectral optoacoustic tomography; MCAO, middle cerebral artery occlusion; HE, hematoxylin and eosin.