While lasers have been commonly used as illumination sources in photoacoustic (PA) imaging, their high purchase and maintenance costs, as well as their bulkiness, have hindered the rapid clinical dissemination of PA imaging. With this in mind, we explore an alternative illumination source for PA tomography—a xenon flash lamp with high pulse energy and a microsecond pulse width. We demonstrate that, by using a single xenon flash lamp, we can image both a black latex cord placed in chicken breast tissue at a depth of up to 3.5 cm ex vivo and an entire mouse body in vivo. Our findings indicate that the xenon flash lamp, producing optical illumination that is safe for humans, can be potentially applied to human tissue imaging.
We demonstrate asymmetric-detection time-stretch optical microscopy which delivers high-contrast (simultaneous enhanced phase-gradient and absorption contrasts) microfluidic imaging with subcellular resolution and in-line optical image amplification (20dB), at a record imaging flow speed of 10 m/s.
Lung cancer is one of the leading causes of cancer mortality worldwide, with an estimated 2.2 million new cancer cases and 1.8 million deaths in 2020. Adenocarcinoma is the most common type of non-small cell lung cancer (NSCLC), which is usually developed with a mixture of histologic subtypes. Surgery to remove the affected tissue or tumor is the most curative treatment option for the early-stage NSCLC currently. The clinical diagnosis of NSCLC based on pathological analysis of formalin-fixed and paraffin-embedded (FFPE) tissues is laborious and time-consuming, failing to guide surgeons intraoperatively. Although frozen section can serve as a rapid alternative to FFPE histology, it still requires a turnaround time of 20–30 minutes during surgery. Besides, the diagnostic accuracy of the frozen section could be affected due to the tissue freezing artifacts and inadequate sampling of resection margins. Here, we propose a rapid histological imaging method, termed microscopy with ultraviolet single-plane illumination (MUSI), which enables label-free and non-destructive imaging of freshly excised and unprocessed tissues. The MUSI system allows the surgical specimens with large irregular surfaces to be scanned in a label-free manner at a speed of 0.65 mm2/s with a subcellular resolution, showing great potential as an assistive imaging platform that can provide immediate feedback to surgeons and pathologists for intraoperative decision-making. We demonstrate that MUSI can differentiate between different subtypes of human lung adenocarcinomas, revealing diagnostically important features that are comparable to the gold standard FFPE histology, holding great promise to revolutionize the current practice of surgical pathology.
Optical imaging based on time-stretch process has recently been proven as a powerful tool for delivering ultra-high frame rate (< 1MHz) which is not achievable by the conventional image sensors. Together with the capability of optical image amplification for overcoming the trade-off between detection sensitivity and speed, this new imaging modality is particularly valuable in high-throughput biomedical diagnostic practice, e.g. imaging flow cytometry. The ultra-high frame rate in time-stretch imaging is attained by two key enabling elements: dispersive fiber providing the time-stretch process via group-velocity-dispersion (GVD), and electronic digitizer. It is well-known that many biophotonic applications favor the spectral window of ~1μm. However, reasonably high GVD (< 0.1 ns/nm) in this range can only be achieved by using specialty single-mode fiber (SMF) at 1μm. Moreover, the ultrafast detection has to rely on the state-of- the-art digitizer with significantly wide-bandwidth and high sampling rate (e.g. <10 GHz, <40 GS/s). These stringent requirements imply the prohibitively high-cost of the system and hinder its practical use in biomedical diagnostics. We here demonstrate two cost-effective approaches for realizing time-stretch confocal microscopy at 1μm: (i) using the standard telecommunication SMF (e.g. SMF28) to act as a few-mode fiber (FMF) at 1μm for the time-stretch process, and (ii) implementing the pixel super-resolution (SR) algorithm to restore the high-resolution (HR) image when using a lower-bandwidth digitizer. By using a FMF (with a GVD of ~ 0.15ns/nm) and a modified pixel-SR algorithm, we can achieve time-stretch confocal microscopy at 1μm with cellular resolution (~ 3μm) at a frame rate 1 MHz.
This paper proposes a fast whole-organ histological imaging method with real-time staining and mechanical sectioning. Time-consuming and laborious sample processing procedures are not needed. The imaged tissue block will be labeled along with the serial sectioning and optical scanning to improve the overall speed and the uniformity of staining. A super-resolution network (ESRGAN) and an optical-sectioning imaging technique (HiLo microscopy) have been applied to optimize the imaging speed and resolution. The proposed system can realize whole-organ histological imaging within hours to days, depending on the volume of the imaged sample.
Optical microscopy is indispensable to biomedical research and clinical investigations. As all molecules absorb light, optical-resolution photoacoustic microscopy (PAM) is an important tool to image molecules at high resolution without labeling. However, due to tissue-induced optical aberration, the imaging quality degrades with increasing imaging depth. To mitigate this effect, we develop an imaging method, called acoustic-feedback wavefront-adapted PAM (AWA-PAM), to dynamically compensate for tissue-induced aberration at depths. In contrast to most existing adaptive optics assisted optical microscopy, AWA-PAM employs acoustic signals rather than optical signals to indirectly determine the optimized wavefront. To demonstrate this technique, we imaged zebrafish embryos and mouse ears in vivo. Experimental results show that compensating for tissue-induced aberration in live tissue effectively improves both signal strength and lateral resolution. With this capability, AWA-PAM reveals fine structures, such as spinal cords and microvessels, that were otherwise unidentifiable using conventional PAM. We anticipate that AWA-PAM will benefit the in vivo imaging community and become an important tool for label-free optical imaging in the quasi-ballistic regime.
Ultraviolet photoacoustic microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 ± 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible photoacoustic image of a mouse brain slice with specific absorption contrast in ∼16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.
We propose a rapid and label-free three-dimensional imaging technique to analyze paraffin-embedded whole organs without tissue staining or clearing. Various anatomical structures are revealed at subcellular resolution, facilitating comprehensive and volumetric cellular histopathological analysis.
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