Contrast-enhanced photoacoustic imaging in the second near-infrared window using semiconducting polymer nanoparticles

Abstract

Photoacoustic imaging (PAI) is a fast growing deep-tissue imaging modality. However, light scattering and absorption in biological tissues limit imaging depth. Short near-infrared wavelengths (650 to 950 nm) are widely used for PAI. Using longer near-infrared wavelengths reduces scattering. We demonstrate deep-tissue contrast-enhanced in vivo photoacoustic imaging at a wavelength of 1064 nm. An ultranarrow bandgap semiconducting polymer poly (thienoisoindigo-alt-diketopyrrolopyrrole) (denoted as PIGD) is designed and demonstrated for imaging at 1064 nm. By embedding colloidal nanoparticles (NPs) of PIGD in chicken-breast tissue, an imaging depth of ∼5 cm is achieved. Intravenous injection of PIGD NPs in living rats showed brain vascular images with ∼2 times higher contrast compared with the brain vascular images without any contrast agent. Thus, PIGD NPs as an NIR-II contrast agent opens new opportunities for both preclinical and clinical imaging of deep tissues with enhanced contrast.

Keywords: biomaterials; brain vascular imaging; deep-tissue imaging; photoacoustic tomography; second near-infrared window.

Fig. 1

(a) Synthesis of conjugated polymer PIGD by direct arylation polymerization, (b) schematic illustration of conjugated PIGD encapsulated by surfactant F127 upon nanoprecipitation in water/THF mixture followed by evaporation of THF, resulting in colloidal nanoparticles with PIGD as the core, PPO as the shell and PEO as the corona, (c) TEM image of air-dried PIGD NPs in water, (d) DLS result of PIGD NPs in water; the inset of (d) is the digit photo of PIGD NPs dispersion under room light, and (e) UV-vis-NIR absorption spectra of PIGD in water.

Fig. 2

(a) Schematic diagram of NIR-II PAT system. Here, M, mirror; CSP, circular scanning plate; MPS, motor pulley system, SM, stepper motor; DAQ, data acquisition card; AU, ultrasound pulser/receiver unit; UST, ultrasound transducer; GG, ground glass; PF, $100\text{-}\mu \mathrm{m}$ transparent polythene membrane; (b) PA signals of PIGD NPs compared with fresh rat blood, and (c) PA amplitude as a function of concentration of PIGD nanoparticles.

Fig. 3

Deep-tissue PA imaging of PIGD NPs embedded inside chicken-breast tissue at 1064 nm. Photograph of the (a) agar gel phantom containing PIGD NPs dots with different concentrations (s1 to s3: 1.0, 0.5, and $0.25\mathrm{mg}/\mathrm{mL}$, respectively), (b) stack of chicken tissue layers on the agar phantom, (c–g) PA images of the agar gel phantom containing PIGD NPs solutions acquired at different depths, (h) SNR with different PIGD NPs concentration as a function of penetration depth inside chicken-breast tissue. Laser energy density used on tissue surface is $\sim 25\mathrm{mJ}/{\mathrm{cm}}^2$.

Fig. 4

In vivo PA imaging of rat brain vasculature: cross-sectional brain vascular images at (a) 0 min (before injection), (b) 40 min-, (c) 70 min postinjection of PIGD NPs. PIGD NP solution ($2\mathrm{mg}/\mathrm{mL}$) was administered via tail vein injection with a dose of 0.25 mL per 100-gm body weight, (d) PA amplitude and SNR (dB) as a function of postinjection time. The blue arrow indicates injection point. Photograph of rat brain before (a) and after (b) removing the scalp. Laser energy density used for brain vascular imaging is $\sim 5\mathrm{mJ}/{\mathrm{cm}}^2$.