Review on photoacoustic imaging of the brain using nanoprobes

Abstract

Photoacoustic (PA) tomography (PAT) is a hybrid imaging modality that integrates rich optical contrasts with a high-ultrasonic spatial resolution in deep tissue. Among various imaging applications, PA neuroimaging is becoming increasingly important as it nicely complements the limitations of conventional neuroimaging modalities, such as the low-temporal resolution in magnetic resonance imaging and the low depth-to-resolution ratio in optical microscopy/tomography. In addition, the intrinsic hemoglobin contrast PA neuroimaging has also been greatly improved by recent developments in nanoparticles (NPs). For instance, near-infrared absorbing NPs greatly enhanced the vascular contrast in deep-brain PAT; tumor-targeting NPs allowed highly sensitive and highly specific delineation of brain tumors; and multifunctional NPs enabled comprehensive examination of the brain through multimodal imaging. We aim to give an overview of NPs used in PA neuroimaging. Classifications of various NPs used in PAT will be introduced at the beginning, followed by an overview of PA neuroimaging systems, and finally we will discuss major applications of NPs in PA neuroimaging and highlight representative studies.

Keywords: nanoparticle; neuroimaging; photoacoustic tomography.

Fig. 1

Schematics of (a) optical-resolution photoacoustic microscopy and (b) acoustic-resolution photoacoustic microscopy.

Fig. 2

Schematics of: (a) cylindrical-view photoacoustic computed tomography (PACT), (b) planar-view PACT, (c) spherical-view PACT, (d) linear-view PACT, and (d) circular-view PACT.

Fig. 3

Noninvasive photoacoustic (PA) neuroimaging employing gold nanoparticles (NPs). (a) and (d) PA images acquired through an intact rat scalp before and 20 min after tail vein injection of gold nanoshells, respectively. The experiment was performed on a single-element–based circular-view PACT system. (c) PA image acquired through an intact mouse scalp after nanostar injection. R: rostral rhinal vein. S: sagittal sinus. T: transverse sinus. (d) PA intensity (normalized to the first frame) of sagittal sinus calculated from each frame. Inset, normalized PA intensity monitored for the initial 600 s. The experiment was performed on an array-based circular-view PACT system. Reproduced with permission from Refs.  and .

Fig. 4

Coronal-view PA images demonstrating the effect of passive tumor targeting with PDI NPs. Images were acquired after tail vein injection of $250\mu \mathrm{L}$ of 250 nM PDI NPs in a mouse with an orthotopic glioblastoma tumor. Adapted with permission from Ref. .

Fig. 5

(a) PA image of an excised rat brain containing a tumor treated with nanoshells. Field of view: $2\mathrm{cm}\times 2\mathrm{cm}$. (b) Photograph of the brain in (a). Adapted with permission from Ref. .

Fig. 6

MPR multimodal images of a mouse brain. (a) Magnetic resonance imaging (MRI) image, (b) PA image (green) superimposed on MRI image, and (c) Raman (red) superimposed on MRI image. Reproduced with permission from Ref. .