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Abstract Photoacoustic microscopy (PAM) systems often face challenges in simultaneously achieving high speed, high resolution, high sensitivity, and a large field of view (FOV). To address this challenge, we have developed dual-channel PAM (DC-PAM) that can expand the FOV without compromising the imaging speed, detection sensitivity, or spatial resolution. DC-PAM has two identical, independent channels of laser excitation and acoustic detection. It exploits two facets of a single hexagon scanner to concurrently steer the dual excitation laser beams and the resultant acoustic waves. DC-PAM achieves an ultra-wide FOV of 22.5 × 24 mm² with a total functional imaging time of ~15 s. Proof-of-concept experiments were conducted using DC-PAM on freely-swimming zebrafish, hypoxia-challenged mice, and sleeping glassfrogs, all of which benefit from the large FOV and high imaging speed to track the dynamic and physiological processes at the whole-organ or whole-body level. These applications demonstrate the potential of DC-PAM for a wide range of biological studies. 

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. 

Nanoparticle-mediated photothermal therapy (PTT) is a promising strategy for cancer treatment; however, nanoparticle instability and lack of precise imaging tools for real-time temperature monitoring during therapy and nanoparticle tracking have hindered investigations in animal models. To address these critical issues, we present a theranostic platform that seamlessly integrates armored core–gold nanostar (AC-GNS)–mediated PTT with full-view photoacoustic computed tomography (PACT), enabling nanoparticle tracking and real-time imaging-guided PTT in deep tissues. The AC-GNS platform delivered exceptional photostability and thermal resilience beyond those of conventional nanoparticles while serving as a high-performance contrast agent for PACT and a photothermal transducer for PTT. Integrating AC-GNS–mediated PTT with noninvasive PACT enabled whole-body nanoparticle tracking, PTT treatment monitoring via thermal imaging, and thermal dose determination, culminating in a 100% survival rate in a murine bladder cancer model without long-term treatment-related toxicity. This theranostic platform lays the foundation for broader research applications and provides opportunities for advancing solid tumor treatment and response assessment research.