Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes.
more »
« less
Eavesdrop at Clinical Depths: Deep Photoacoustic Imaging with Internal Light Illumination
Photoacoustic imaging (PAI) is a hybrid image modality that combines optical absorption contrast and acoustic detection of light-induced ultrasound waves. PAI can produce high-resolution and molecular-sensitive images of deep tissues, which are useful for various preclinical studies, such as brain functions, cancer therapy, and vascular imaging. However, PAI faces the challenge of strong optical attenuation in biological tissues, which limits the imaging depth of conventional PAI to several centimeters. Many clinically relevant organs are located near body cavities, which offers the opportunity to navigate a catheter-based device for internal-illumination PAI. By delivering light directly to the target through an optical fiber, internal-illumination PAI can effectively overcome the optical attenuation problem and achieve imaging depths of more than 10 cm while maintaining the resolution, signal-to-noise ratio, and functional and molecular sensitivity of PAI. Thus, internal-illumination PAI has great potential for medical applications. This review introduces the principles and applications of different internal-illumination PAI modalities: photoacoustic endoscopy, internal-illumination photoacoustic tomography, and photoacoustic-guided ablation. We highlight the current research directions and challenges and discuss the future opportunities.
more »
« less
- Award ID(s):
- 2144788
- PAR ID:
- 10668616
- Publisher / Repository:
- Science
- Date Published:
- Journal Name:
- Advanced Devices & Instrumentation
- Volume:
- 6
- ISSN:
- 2767-9713
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Endoscopy, enabling high-resolution imaging of deep tissues and internal organs, plays an important role in basic research and clinical practice. Recent advances in photoacoustic microscopy (PAM), demonstrating excellent capabilities in high-resolution functional imaging, have sparked significant interest in its integration into the field of endoscopy. However, there are challenges in achieving functional PAM in the endoscopic setting. This Perspective article discusses current progress in the development of endoscopic PAM and the challenges related to functional measurements. Then, it points out potential directions to advance endoscopic PAM for functional imaging by leveraging fiber optics, microfabrication, optical engineering, and computational approaches. Finally, it highlights emerging opportunities for functional endoscopic PAM in basic and translational biomedicine.more » « less
-
Metabolic imaging is critical for understanding cellular functions beyond morphology, offering significant insights into various biological processes and disease states. Label-free optical imaging techniques stand out by providing high-resolution, molecularly specific, and/or non-invasive assessments of metabolic activity without relying on exogenous contrast agents. This review discusses the key photon-tissue interactions—absorption, emission, and scattering—that underpin label-free optical imaging modalities for interrogating tissue’s metabolic activities at various scales. Specifically, photoacoustic imaging (PAI) leverages absorption-based contrasts such as hemoglobin oxygenation and glucose concentrations to quantify metabolic dynamics. Emission-based techniques, including two-photon fluorescence (TPF) and fluorescence lifetime imaging microscopy (FLIM), exploit intrinsic fluorophores like nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) to assess cellular energy metabolism. Interferometric methods, particularly optical coherence tomography (OCT), provide insights into tissue morphological changes. Second harmonic generation (SHG) detects extracellular matrix components such as the collagen network. Molecular vibrational imaging methods, such as stimulated Raman scattering (SRS) microscopy, visualizes spatial heterogeneity of molecular compositions. Recent clinical translations of these methods highlight their growing roles in oncology, neurology, and dermatology, underscoring their potential in early disease diagnosis and monitoring therapeutic responses. Despite challenges such as depth limitations, advancements like wavefront engineering and optical clearing techniques promise to enhance imaging penetration and clinical applicability, paving the way for broader adoption of label-free optical metabolic imaging in both research and clinical settings.more » « less
-
Intraoperative imaging of slide-free specimens is crucial for oncology surgeries, allowing surgeons to quickly identify tumor margins for precise surgical guidance. While high-resolution ultraviolet photoacoustic microscopy has been demonstrated for slide-free histology, the imaging speed is insufficient, due to the low laser repetition rate and the limited depth of field. To address these challenges, we present parallel ultraviolet photoacoustic microscopy (PUV-PAM) with simultaneous scanning of eight optical foci to acquire histology-like images of slide-free fresh specimens, improving the ultraviolet PAM imaging speed limited by low laser repetition rates. The PUV-PAM has achieved an imaging speed of 0.4 square millimeters per second (i.e., 4.2 minutes per square centimeter) at 1.3-micrometer resolution using a 50-kilohertz laser. In addition, we demonstrated the PUV-PAM with eight needle-shaped beams for an extended depth of field, allowing fast imaging of slide-free tissues with irregular surfaces. We believe that the PUV-PAM approach will enable rapid intraoperative photoacoustic histology and provide prospects for ultrafast optical-resolution PAM.more » « less
-
Abstract Optical‐resolution photoacoustic microscopy (OR‐PAM) has been increasingly utilized for in vivo imaging of biological tissues, offering structural, functional, and molecular information. In OR‐PAM, it is often necessary to make a trade‐off between imaging depth, lateral resolution, field of view, and imaging speed. To improve the lateral resolution without sacrificing other performance metrics, we developed a virtual‐point‐based deconvolution algorithm for OR‐PAM (VP‐PAM). VP‐PAM has achieved a resolution improvement ranging from 43% to 62.5% on a single‐line target. In addition, it has outperformed Richardson‐Lucy deconvolution with 15 iterations in both structural similarity index and peak signal‐to‐noise ratio on an OR‐PAM image of mouse brain vasculature. When applied to an in vivo glass frog image obtained by a deep‐penetrating OR‐PAM system with compromised lateral resolution, VP‐PAM yielded enhanced resolution and contrast with better‐resolved microvessels.more » « less
An official website of the United States government

