Photoacoustic imaging (PAI) is an emerging biomedical imaging modality that is based on optical absorption contrast, capable of revealing distinct spectroscopic signatures of tissue at high spatial resolution and large imaging depths. However, clinical applications of conventional non-invasive PAI systems have been restricted to examinations of tissues at depths less than a few cm due to strong light attenuation. Minimally invasive photoacoustic imaging (miPAI) has greatly extended the landscape of PAI by delivering excitation light within tissue through miniature fibre-optic probes. In the past decade, various miPAI systems have been developed with demonstrated applicability in several clinical fields. In this article, we present an overview of the current status of miPAI and our thoughts on future perspectives.

Multimode fibres (MMFs) are becoming increasingly attractive in optical endoscopy as they promise to enable unparallelled miniaturisation, spatial resolution and cost. However, high-speed imaging with wavefront shaping has been challenging. Here, we report the development of a video-rate dual-modal photoacoustic (PA) and fluorescence microscopy probe with a high-speed digital micromirror device (DMD) towards forward-viewing endomicroscopy. Optimal DMD patterns were obtained using a real-valued intensity transmission matrix algorithm to raster-scan a 1.5 $\mathrm{\mu }$m-diameter focused beam at the distal fibre tip for imaging. The PA imaging speed and spatial resolution were varied from $\sim$2 to 57 frames per second and from 1.7 to 3 $\mathrm{\mu }$m, respectively. Further, high-fidelity PA images of carbon fibres and mouse red blood cells were acquired at unprecedented speed. The capability of dual-modal imaging was demonstrated with phantoms. We anticipate that with further miniaturisation of the ultrasound detector, this probe could be integrated into medical needles to guide minimally invasive procedures.

Ultrasound is an essential tool for guidance of many minimally-invasive surgical and interventional procedures, where accurate placement of the interventional device is critical to avoid adverse events. Needle insertion procedures for anaesthesia, fetal medicine and tumour biopsy are commonly ultrasound-guided, and misplacement of the needle may lead to complications such as nerve damage, organ injury or pregnancy loss. Clear visibility of the needle tip is therefore critical, but visibility is often precluded by tissue heterogeneities or specular reflections from the needle shaft. This paper presents the in vitro and ex vivo accuracy of a new, real-time, ultrasound needle tip tracking system for guidance of fetal interventions. A fibre-optic, Fabry-Pérot interferometer hydrophone is integrated into an intraoperative needle and used to localise the needle tip within a handheld ultrasound field. While previous, related work has been based on research ultrasound systems with bespoke transmission sequences, the new system—developed under the ISO 13485 Medical Devices quality standard—operates as an adjunct to a commercial ultrasound imaging system and therefore provides the image quality expected in the clinic, superimposing a cross-hair onto the ultrasound image at the needle tip position. Tracking accuracy was determined by translating the needle tip to 356 known positions in the ultrasound field of view in a tank of water, and by comparison to manual labelling of the the position of the needle in B-mode US images during an insertion into an ex vivo phantom. In water, the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a mean repeatability of 0.3 ± 0.2 mm. In the tissue phantom, the mean distance between tracked and labelled positions was 1.1 ± 0.7 mm. Tracking performance was found to be independent of needle angle. The study demonstrates the performance and clinical compatibility of ultrasound needle tracking, an essential step towards a first-in-human study.

Photoacoustic endoscopy (PAE) can provide 3D functional, molecular and structural information of tissue deep inside the human body, and thus could be well suited for guiding minimally invasive procedures such as tumour biopsy and fetal surgery. One of the major challenges in the development of miniature PAE probes, in particular, forward-viewing PAE probes, is the integration of a sensitive and broadband ultrasound sensor with the light delivery and scanning system into a small footprint. In this work, we developed a forward-viewing PAE probe enabling optical-resolution microscopy imaging based on a transparent ultrasound sensor coated on the distal end of a multimode optical fibre. The transparent sensor comprised a transparent polyvinylidene fluoride (PVDF) thin film coated with indium tin oxide (ITO) electrodes with a diameter of 2 mm. Excitation laser light was focused and raster-scanned across the facet of the probe tip through the multimode fibre and the PVDF-ITO thin film via wavefront shaping. The sensor had an optical transmission rate of 55–72% in the wavelength range of 400 to 800 nm, a centre frequency of 17.5 MHz and a −10 dB bandwidth of 25 MHz. Singular value decomposition was used to remove a prominent trigger-induced noise, which enabled imaging close to the probe tip with an optically defined lateral resolution of 2 µm. The performance of the imaging probe was demonstrated by obtaining high-fidelity photoacoustic microscopy images of carbon fibres. With further optimisation of the sensitivity, the probe promises to guide minimally invasive procedures by providing in situ, in vivo characterisation of tissue.

Photoacoustic (PA) endoscopy promises to be useful in a variety of clinical contexts including intravascular imaging, gastrointestinal tracts imaging and surgical guidance. Recent advancements of optical wavefront shaping allow the development of ultrathin endoscopy probes based on multimode optical fibres, which can provide higher spatial resolution than previously reported fibre bundle-based endoscopes. In this work, we developed a forward-viewing PA endomicroscopy imaging system and further improved its performance with a deep image prior (DIP) neural network. Laser was focused and scanned through a multimode fibre via wavefront shaping, in which a real-valued intensity transmission matrix approach was used for fibre characterisation, and a digital micromirror device (DMD) was used for light modulation. The excited ultrasound waves at the distal fibre tip were detected by an ultrasound transducer. High fidelity images of ex vivo mouse red blood cells were acquired. A DIP neural network was then used to improve the spatial resolution with unsupervised learning. Convolutional filters were used to learn features of low-level images as priors and reconstruct high-resolution images accordingly. The performance of the DIP approach was evaluated using a structural similarity index measure (SSIM) at a level of 0.85 with 25% effective pixels, which outperformed the bicubic method. The use of DIP allows reducing scanning positions by several times, and thus improves the speed of pixel-wise PA microscopy imaging. With further miniaturisation of the ultrasound detector, we anticipate that this system could be used for real-time guidance of minimally invasive surgeries by providing micro-structural, molecular, and functional information of tissue.

Precise light delivery through biological tissue is essential for deep-tissue imaging and phototherapeutic applications. Wavefront shaping enables control over scattered light by modulating the incident wavefront, but its application in living tissue is hindered by tissue-induced temporal decorrelation. This study systematically investigated the real-valued intensity transmission matrix (RVITM), a high-speed wavefront shaping method, for light focusing across a broad range of speckle decorrelation times. The inherent trade-off between static light focusing enhancement and implementation speed is characterized, which provided practical guidelines for implementing RVITM in real-time wavefront shaping under varying dynamic conditions. Effective optical focusing using a RVITM with 33 ms runtime was achieved through porcine liver with decorrelation times as short as 13 ms, demonstrating feasibility for biologically relevant dynamics and supporting the development of adaptive, non-invasive optical control for biomedical applications.