Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects.

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.

A wearable cardiac ultrasound imager.

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.

A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature.

Electronic patches, based on various mechanisms, allow continuous and noninvasive monitoring of biomolecules on the skin surface. However, to date, such devices are unable to sense biomolecules in deep tissues, which have a stronger and faster correlation with the human physiological status than those on the skin surface. Here, we demonstrate a photoacoustic patch for three-dimensional (3D) mapping of hemoglobin in deep tissues. This photoacoustic patch integrates an array of ultrasonic transducers and vertical-cavity surface-emitting laser (VCSEL) diodes on a common soft substrate. The high-power VCSEL diodes can generate laser pulses that penetrate >2 cm into biological tissues and activate hemoglobin molecules to generate acoustic waves, which can be collected by the transducers for 3D imaging of the hemoglobin with a high spatial resolution. Additionally, the photoacoustic signal amplitude and temperature have a linear relationship, which allows 3D mapping of core temperatures with high accuracy and fast response. With access to biomolecules in deep tissues, this technology adds unprecedented capabilities to wearable electronics and thus holds significant implications for various applications in both basic research and clinical practice.

Detection of Kidney Dysfunction through In Vivo Magnetic Resonance Imaging with Renal-Clearable Gadolinium Nanoprobes.

Kidney dysfunction is a clinical syndrome that can subsequently result in lethal kidney failure. The exploration of emerging bioimaging contrast agents with translational potential is highly challenging for a feasible diagnosis of kidney dysfunction. Herein, a class of renal-clearable gadolinium nanoparticles (Gd@PEG NPs) with an ultrasmall size of ∼5 nm, good monodispersity, and T1 relaxivity are synthesized using mesoporous silica nanoparticles as the template. Assisted by such renal-clearable Gd@PEG NPs, the diagnosis of kidney dysfunction in a mice model with a damaged kidney has been achieved through in vivo noninvasive magnetic resonance imaging. As a result, this work paves the way to synthesize monodispersible ultrasmall Gd contrast agents, facilitating the exploration of translational strategies for an in vivo analysis of kidney dysfunction.

Facile and Controllable Synthesis of the Renal-Clearable "Luminous Pearls" for in Vivo Afterglow/Magnetic Resonance Imaging.

To date, the strategic exploration of a synthetic approach to afford persistent luminescent nanoparticles (PLNPs) integrated with precisely controlled size/monodispersity and renal-clearable capability remains extremely challenging. Herein, we report a facile synthetic process with an elucidated mechanism to fine-tune the size for acquiring renal-clearable PLNPs, using mesoporous silica nanoparticles (MSNs) as a template. This strategy relies on the controlled crystallization of the precursor ions in the pore channels of MSNs at a high temperature, leading to the formation of monodispersed PLNPs with an average diameter as small as 2.5 nm after complete removal of MSN templates. The as-prepared ultrasmall PLNPs coated with polyethylene glycol exhibit uniform size, excellent water-dispersibility, good persistent luminescence, and high T1 relaxivity (17.6 mM-1·S-1), ensuring their suitability for afterglow/magnetic resonance dual-modality imaging and subsequent in vivo renal clearance. Thus, our study provides a strategy to inspire the controlled synthesis of diverse PLNPs by using MSN templates, simultaneously addressing the critical issues of precise adjustment of size and body clearance for versatile biomedical applications.

Nanoparticle-based Cell Trackers for Biomedical Applications.

The continuous or real-time tracking of biological processes using biocompatible contrast agents over a certain period of time is vital for precise diagnosis and treatment, such as monitoring tissue regeneration after stem cell transplantation, understanding the genesis, development, invasion and metastasis of cancer and so on. The rationally designed nanoparticles, including aggregation-induced emission (AIE) dots, inorganic quantum dots (QDs), nanodiamonds, superparamagnetic iron oxide nanoparticles (SPIONs), and semiconducting polymer nanoparticles (SPNs), have been explored to meet this urgent need. In this review, the development and application of these nanoparticle-based cell trackers for a variety of imaging technologies, including fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, magnetic particle imaging, positron emission tomography and single photon emission computing tomography are discussed in detail. Moreover, the further therapeutic treatments using multi-functional trackers endowed with photodynamic and photothermal modalities are also introduced to provide a comprehensive perspective in this promising research field.