Photoacoustic tomography (PAT), also called optoacoustic tomography, is a three-dimensional (3-D) imaging modality based on the photoacoustic (PA) effect. Although the PA effect was discovered more than a century ago by Alexander Graham Bell, it has found applications in biomedical imaging only in the last decade or so. Nowadays, PAT is one of the largest research areas in biomedical optics and is still growing rapidly.¹

Photoacoustic tomography (PAT) is a hybrid imaging modality that combines rich contrast of optical excitation and deep penetration of ultrasound detection. With its unique optical absorption contrast mechanism, PAT is inherently sensitive to the functional and molecular information of biological tissues, and thus has been widely used in preclinical and clinical studies. Among many functional capabilities of PAT, measuring blood oxygenation is arguably one of the most important applications, and has been widely performed in photoacoustic studies of brain functions, tumor hypoxia, wound healing, and cancer therapy. Yet, the complex optical conditions of biological tissues, especially the strong wavelength-dependent optical attenuation, have long hurdled the PAT measurement of blood oxygenation at depths beyond a few millimeters. A variety of PAT methods have been developed to improve the accuracy of blood oxygenation measurement, using novel laser illumination schemes, oxygen-sensitive fluorescent dyes, comprehensive mathematic models, or prior information provided by complementary imaging modalities. These novel methods have made exciting progress, while several challenges remain. This concise review aims to introduce the recent developments in photoacoustic blood oxygenation measurement, compare each method's advantages and limitations, highlight their representative applications, and discuss the remaining challenges for future advances.

Almost all diseases, especially cancer and diabetes, manifest abnormal oxygen metabolism. Accurately measuring the metabolic rate of oxygen (MRO₂) can be helpful for fundamental pathophysiological studies, and even early diagnosis and treatment of disease. Current techniques either lack high resolution or rely on exogenous contrast. Here, we propose label-free metabolic photoacoustic microscopy (mPAM) with small vessel resolution to noninvasively quantify MRO₂in vivo in absolute units. mPAM is the unique modality for simultaneously imaging all five anatomical, chemical, and fluid-dynamic parameters required for such quantification: tissue volume, vessel cross-section, concentration of hemoglobin, oxygen saturation of hemoglobin, and blood flow speed. Hyperthermia, cryotherapy, melanoma, and glioblastoma were longitudinally imaged in vivo. Counterintuitively, increased MRO₂ does not necessarily cause hypoxia or increase oxygen extraction. In fact, early-stage cancer was found to be hyperoxic despite hypermetabolism.

Human brain mapping has become one of the most exciting contemporary research areas, with major breakthroughs expected in the coming decades. Modern brain imaging techniques have allowed neuroscientists to gather a wealth of anatomic and functional information about the brain. Among these techniques, by virtue of its rich optical absorption contrast, high spatial and temporal resolutions, and deep penetration, photoacoustic tomography (PAT) has attracted more and more attention, and is playing an increasingly important role in brain studies. In particular, PAT complements other brain imaging modalities by providing high-resolution functional and metabolic imaging. More importantly, PAT’s unique scalability enables scrutinizing the brain at both microscopic and macroscopic scales, using the same imaging contrast. In this review, we present the state-of-the-art PAT techniques for brain imaging, summarize representative neuroscience applications, outline the technical challenges in translating PAT to human brain imaging, and envision potential technological deliverables.

High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO₂) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm³ with a high spatial resolution of ~10 μm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain’s fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

Volumetric printing, an emerging additive manufacturing technique, builds objects with enhanced printing speed and surface quality by forgoing the stepwise ink-renewal step. Existing volumetric printing techniques almost exclusively rely on light energy to trigger photopolymerization in transparent inks, limiting material choices and build sizes. We report a self-enhancing sonicated ink (or sono-ink) design and corresponding focused-ultrasound writing technique for deep-penetration acoustic volumetric printing (DAVP). We used experiments and acoustic modeling to study the frequency and scanning rate–dependent acoustic printing behaviors. DAVP achieves the key features of low acoustic streaming, rapid sonothermal polymerization, and large printing depth, enabling the printing of volumetric hydrogels and nanocomposites with various shapes regardless of their optical properties. DAVP also allows printing at centimeter depths through biological tissues, paving the way toward minimally invasive medicine.