Tremendous progress in synthetic micro/nanomotors has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control in vivo. Here, we present a photoacoustic computed tomography (PACT) guided investigation of micromotors in intestines in vivo. The micromotors enveloped in microcapsules exhibit efficient propulsion in various biofluids once released. PACT has visualized the migration of micromotor capsules toward the targeted regions in real time in vivo. The integration of the developed microrobotic system and PACT enables deep imaging and precise control of the micromotors in vivo.
Photoacoustic (PA) computed tomography (PACT) is a non-invasive imaging technique offering optical contrast, high resolution, and deep penetration in biological tissues. PACT, highly sensitive to optical absorption by molecules, is inherently suited for molecular imaging using optically absorbing probes. Genetically encoded probes with photochromic behavior dramatically increase detection sensitivity and specificity of PACT through photoswitching and differential imaging. Starting with a DrBphP bacterial phytochrome, we have engineered a near-infrared photochromic probe, DrBphP-PCM, which is superior to the full-length RpBphP1 phytochrome previously used in differential PACT. DrBphP-PCM has a smaller size, better folding, and higher photoswitching contrast. We have also developed an advanced PACT technique, which combines the reversibly-switchable photochromic probes with single-impulse panoramic PACT, termed RS-SIP-PACT. Using RS-SIP-PACT, we have characterized DrBphP-PCM both in vitro and in vivo as an advanced near-infrared photochromic probe for PACT. We introduce two phytochromes into the same mammalian cells, resulting in a distinctive decay characteristic in comparison with the cells expressing DrBphP-PCM only. By discriminating the different decay characteristics, we successfully separate multiple cell types in deep tissues. The simple structural organization of DrBphP-PCM allows engineering a bimolecular PA complementation reporter, a split version of DrBphP-PCM, termed DrSplit. DrSplit enables PA detection of protein-protein interactions in deepseated mouse tumors and livers, achieving 125-μm spatial resolution and 530-cell sensitivity in vivo. The combination of RS-SIP-PACT with DrBphP-PCM and DrSplit holds great potential for non-invasive multi-contrast deep-tissue functional imaging.
We present a method of imaging angiographic structures in human extremities, including hands, arms, legs, and feet, using a newly developed photoacoustic computed tomography (PACT) system. The system features deep penetration (1.8 cm in muscular tissues) with high spatial and temporal resolutions. A volumetric image is acquired within 5 to 15 s while each cross sectional image is acquired within 100 μs. Therefore, we see no blurring from motion in the imaging plane. Longitudinal and latitudinal cross-sectional images of a healthy volunteer clearly show the vascular network of each appendage and highlight the system’s ability to image major and minor vasculatures, without the use of an external contrast or ionizing radiation. We also track heartbeat-induced arterial movement at a two-dimensional frame rate of 10 Hz. This work substantiates the idea that PACT could be used as a noninvasive method for imaging human vasculatures.
Photoacoustic endoscopy offers in vivo examination of the visceral tissue using endogenous contrast, but its typical B-scan rate is ∼10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250-Hz B-scan rate over a 3-mm scanning range. Using this modality, we not only illustrated the morphological differences of vasculatures among the human ectocervix, uterine body, and sublingual mucosa but also showed the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.
Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth.
We have developed a single-breath-hold photoacoustic computed tomography (SBH-PACT) system to detect tumors and reveal detailed angiographic information about human breasts. SBH-PACT provides high spatial and temporal resolutions with a deep in vivo penetration depth of over 4 cm. A volumetric breast image can be acquired by scanning the breast within a single breath hold (~15 sec). We imaged a healthy female volunteer and seven breast cancer patients. SBH-PACT clearly identified all tumors by revealing higher blood vessel densities and lower compliance associated with the tumors