Photoacoustic Imaging in Tissue Engineering and Regenerative Medicine

Abstract

Several imaging modalities are available for investigation of the morphological, functional, and molecular features of engineered tissues in small animal models. While research in tissue engineering and regenerative medicine (TERM) would benefit from a comprehensive longitudinal analysis of new strategies, researchers have not always applied the most advanced methods. Photoacoustic imaging (PAI) is a rapidly emerging modality that has received significant attention due to its ability to exploit the strong endogenous contrast of optical methods with the high spatial resolution of ultrasound methods. Exogenous contrast agents can also be used in PAI for targeted imaging. Applications of PAI relevant to TERM include stem cell tracking, longitudinal monitoring of scaffolds in vivo, and evaluation of vascularization. In addition, the emerging capabilities of PAI applied to the detection and monitoring of cancer and other inflammatory diseases could be exploited by tissue engineers. This article provides an overview of the operating principles of PAI and its broad potential for application in TERM. Impact statement Photoacoustic imaging, a new hybrid imaging technique, has demonstrated high potential in the clinical diagnostic applications. The optical and acoustic aspect of the photoacoustic imaging system works in harmony to provide better resolution at greater tissue depth. Label-free imaging of vasculature with this imaging can be used to track and monitor disease, as well as the therapeutic progression of treatment. Photoacoustic imaging has been utilized in tissue engineering to some extent; however, the full benefit of this technique is yet to be explored. The increasing availability of commercial photoacoustic systems will make application as an imaging tool for tissue engineering application more feasible. This review first provides a brief description of photoacoustic imaging and summarizes its current and potential application in tissue engineering.

Keywords: assessment; cell tracking and monitoring; label-free vascular imaging; photoacoustic imaging; scaffold imaging; tissue engineering.

FIG. 1.

OR-PAM of relative total hemoglobin concentration (HbT) in a living mouse ear, revealing the vascular anatomy. Insert shows a densely packed capillary bed and individual red blood cells traveling along a capillary. © 2011 Reprinted with permission of Optical Society of America. OR-PAM, optical-resolution PAM. Color images are available online.

FIG. 2.

Absorbance spectra of endogenous contrast agents. © 2012 Reprinted with permission from iThera Medical, Inc. Color images are available online.

FIG. 3.

Metabolic PAM images. (A) Metabolic PAM image of total concentration of hemoglobin (CHb) (B) metabolic image of hemoglobin oxygen saturation (sO₂) of area inside the dashed box (C) Red arrow indicates positive scanning direction, and blue arrow indicates negative scanning direction and (D) Speed of blood flow across the dashed line in (C). Scale bar: (A) 500 μm (B, C) 125 μm. © 2011 Reprinted with permission from Society of Photo-Optical Instrumentation Engineers (SPIE). Color images are available online.

FIG. 4.

PA imaging of scaffolds. US-PA images of PLGA (A–C) and SWNT-PLGA (D–F) scaffolds imaged at 680 nm embedded into chicken breast tissue at depths of (A, D) 0.5 mm (B, E) 2 mm and (C, F) 6 mm (G) 3D US-PA image rendition of SWNT-PLGA scaffolds embedded 0.5 mm in chicken breast tissue (H) US/PA amplitude scale is shown. © 2014 Reprinted with permission from Mary Ann Liebert. 3D, three-dimensional; PLGA, poly(lactic-co-glycolic acid); US-PA, ultrasound-photoacoustic. Color images are available online.

FIG. 5.

PA imaging in cell tracking and monitoring. PA images of burn tissue treated with ASCs. ASCs were labeled with gold nanorods for PA contrast. Spectroscopic PA imaging allowed to identify and track ASCs over the period of 14 days. Oxygen saturation (oxygenated-red and deoxygenated-blue) indicated wound healing or tissue regeneration process. © Reprinted with permission of Mary Ann Liebert. ASCs, adipose-derived stem cells. Color images are available online.

FIG. 6.

(A) Label free imaging of angiogenesis at varying depths at different time points using PA imaging. © 2015 Reprinted with permission of AME. (B) PA images of blood vessels after cold (left) and warm (right) stimulus. © 2018 Reprinted with permission of Springer Berlin Heidelberg. Color images are available online.