Sound out the impaired perfusion: Photoacoustic imaging in preclinical ischemic stroke

Abstract

Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes.

Keywords: blood oxygenation; brain perfusion; functional brain imaging; ischemic stroke; photoacoustic computed tomography; photoacoustic imaging; photoacoustic microscopy.

FIGURE 1

Fundamental principle of PAI.

FIGURE 2

PAI of single vessel occlusions (Lin et al., 2017; Cai et al., 2022). (A) PAM (top row) and PACT (bottom row) images of a blood vessel before PT stroke, after PT stroke, and after experimental tPA treatment, acquired at 720nm. (B) PAM images of a blood vessel before and after PT stroke acquired at 532nm with corresponding blood flow velocity calculations on the left. P indicates the parent vessel of the clot, with D1 and D2 indicating two branching daughter vessels.

FIGURE 3

Multi-scale PAI for small-animal stroke research. (A) OR-PAM oxygen saturation of hemoglobin (sO₂) image of mouse brain before stroke, 330s and 411s after stroke (skull removed) (Zhu et al., 2022). (B) AR-PAM image of mouse brain before and after stroke (skull removed) (Deng et al., 2012). (C) (Top) Baseline and post stroke MRI and corresponding PACT images of mouse brain. Infarct region in MRI corresponds with increased deoxygenated blood in PACT (scalp and skull intact) (Lv et al., 2020). (Bottom) Corresponding triphenyltetrazolium chloride (TTC) stained coronal slices and PACT sO₂ coronal images of mouse brain. Deoxygenated region in sO₂ image corresponds with infarct region identified by TTC (scalp and skull intact) (Menozzi et al.).

FIGURE 4

Structural and functional PACT images of a neonatal pig in vivo with PT stroke (Kang et al., 2022). (Left) TTC staining of harvested brain (post-imaging) with dotted regions indicating the regions-of-interest (ROI) for imaging. (Middle) PACT image of total hemoglobin concentration of a transverse brain section, showing the stroke-induced hypoperfusion, with the stroke-infarct ROI marked by the dashed line. SSS, superior sagittal sinus. (Right) Corresponding PA image of the blood oxygenation, showing the stroke-induced tissue hypoxia.

FIGURE 5

MRI, MRA, and PACT images of the brain of a hemicraniectomy patient (Na et al., 2022). (Left) Representative transverse MRI slice with fMRI data overlaid. (Middle) PACT vasculature of the brain. (Right) Corresponding MRA vasculature of the brain. Scalp vessel (Vs), cortical vessel (Vc), and superficial temporal arteries (STA) were used for comparison between MRA and PACT.

FIGURE 6

Major technological challenges of PAI in ischemic stroke research. Technological challenges are shown in red boxes with existing and potential solutions shown in green boxes.