Nonlinearly enhanced photoacoustic microscopy by picosecond-laser-pumped excited state absorption of phthalocyanine nanoprobes

Abstract

Efficient nanoprobes with unique optical properties are highly desirable for good-performance photoacoustic (PA) molecular imaging. The conventionally used PA nanoprobes basically take their ground-state absorption with contrast to the indelible wideband background absorption as the imaging mechanism, thus severely limiting the imaging contrast and sensitivity in practical applications. Herein, a nonlinearly enhanced PA microscopy mechanism with suppressed background interference and improved brightness has been proposed, by distinctively exploiting the picosecond-laser-pumped excited state absorption of the tin phthalocyanine (SnPc) nanoprobes that exhibit strong reverse saturable absorption below the laser damage threshold of tissues. Both theoretical simulation and experimental investigation have been performed to verify the nonlinearly enhanced optical and PA properties of the SnPc nanoprobes with comparison to conventional PA contrast agents. The enhanced PA imaging capability of the SnPc nanoprobes with improved sensitivity and contrast has been demonstrated by tissue-mimicking phantoms and in vivo mouse models. This work revolutionizes the traditional contrast mechanism of PA nanoprobes by introducing picosecond-laser-pumped nonlinear optical nanomaterials, which prefigures great potential for biosensing and bioimaging with improved contrast and sensitivity.

Optical, Electrochemical, Third-Order Nonlinear Optical Investigations of 3,4,5-Trimethoxy Phenyl Substituted Non-Aqueous Phthalocyanines

“…They observed two-photon and three-photon absorption and reported coefficients of β eff 312 cmGW −1 and a γ eff 8.8 cm 3 GW −2 . Phthalocyanine nanoprobes were reported recently, and they have been demonstrated as highly desirable for photoacoustic molecular imaging (Li et al, 2021). Two-photon absorption coefficients of ∼10 −13 cm/W were reported for phthalocyanine porphyrin conjugates metalated with nickel by Xiao et al, 2016.…”

Quantitative 3D Temperature Rendering of Deep Tumors by a NIR-II Reversibly Responsive W-VO2@PEG Photoacoustic Nanothermometer to Promote Precise Cancer Photothermal Therapy

“…As an emerging imaging technology, photoacoustic (PA) imaging combines the excellent contrast of optical imaging with the good tissue penetration of ultrasound through the conversion of photons to acoustic waves, − and it has attracted tremendous attention in the biomedical field. Specifically, aided by a variety of nanomaterials with diversified morphologies and functions, PA imaging had been explored in depth with extended imaging function such as target molecule tracing, cellular environment monitoring, and specific contrast enhancement. − In recent years, studies and experiments have shown that PA technology is capable of monitoring temperature in vivo based on the Grueneisen effect, where the PA signal amplitude grows linearly with temperature in a certain range. − However, as the PA amplitude enhancement in tissue arising from the Grueneisen effect is quite small (∼4% enhancement for 1 °C temperature increase), − the sensitivity and accuracy of the existing method still cannot satisfy the need for precise 3D temperature monitoring in deep-seated tissue.…”

Temporal Evolution of Refractive Index Induced by Short Laser Pulses Accounting for Both Photoacoustic and Photothermal Effects

“…Understanding interactions between light and medium is a longstanding issue in biomedical imaging [1,2], as it has fundamental importance to imaging techniques such as photoacoustic imaging [3][4][5][6]. Optical resolution photoacoustic microscopy (ORPAM) is a photoacoustic imaging modality, which has demonstrated diffraction-limited lateral resolution on the surface [7], subwavelength-resolution label-free imaging [8], and subdiffraction label-free imaging [9], despite typically limited penetration depth of 1-2 mm due to the tight optical focus of ballistic photons [10].…”