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Solvated electrons are powerful reducing agents capable of driving some of the most energetically expensive reduction reactions. Their generation under mild and sustainable conditions remains challenging though. Using near-ultraviolet irradiation under low-intensity one-photon conditions coupled with electrochemical and optical detection, we show that the yield of solvated electrons in water is increased more than 10 times for nanoparticle-decorated electrodes compared to smooth silver electrodes. Based on the simulations of electric fields and hot carrier distributions, we determine that hot electrons generated by plasmons are injected into water to form solvated electrons. Both yield enhancement and hot carrier production spectrally follow the plasmonic near-field. The ability to enhance solvated electron yields in a controlled manner by tailoring nanoparticle plasmons opens up a promising strategy for exploiting solvated electrons in chemical reactions.
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Elétrons , Nanopartículas , Luz , Raios Ultravioleta , ÁguaRESUMO
Neurons of the peripheral nervous system (PNS) are tasked with diverse roles, from encoding touch, pain, and itch to interoceptive control of inflammation and organ physiology. Thus, technologies that allow precise control of peripheral nerve activity have the potential to regulate a wide range of biological processes. Noninvasive modulation of neuronal activity is an important translational application of focused ultrasound (FUS). Recent studies have identified effective strategies to modulate brain circuits; however, reliable parameters to control the activity of the PNS are lacking. To develop robust noninvasive technologies for peripheral nerve modulation, we employed targeted FUS stimulation and electrophysiology in mouse ex vivo skin-saphenous nerve preparations to record the activity of individual mechanosensory neurons. Parameter space exploration showed that stimulating neuronal receptive fields with high-intensity, millisecond FUS pulses reliably and repeatedly evoked one-to-one action potentials in all peripheral neurons recorded. Interestingly, when neurons were classified based on neurophysiological properties, we identified a discrete range of FUS parameters capable of exciting all neuronal classes, including myelinated A fibers and unmyelinated C fibers. Peripheral neurons were excited by FUS stimulation targeted to either cutaneous receptive fields or peripheral nerves, a key finding that increases the therapeutic range of FUS-based peripheral neuromodulation. FUS elicited action potentials with millisecond latencies compared with electrical stimulation, suggesting ion channelmediated mechanisms. Indeed, FUS thresholds were elevated in neurons lacking the mechanically gated channel PIEZO2. Together, these results demonstrate that transcutaneous FUS drives peripheral nerve activity by engaging intrinsic mechanotransduction mechanisms in neurons [B. U. Hoffman, PhD thesis, (2019)].
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Canais Iônicos , Neurônios , Sistema Nervoso Periférico , Estimulação Elétrica Nervosa Transcutânea , Potenciais de Ação , Animais , Interneurônios , Mamíferos , Neurônios/fisiologia , Sistema Nervoso Periférico/fisiologia , Ultrassonografia/métodosRESUMO
The performance of photocatalysts and photovoltaic devices can be enhanced by energetic charge carriers produced from plasmon decay, and the lifetime of these energetic carriers greatly affects overall efficiencies. Although hot electron lifetimes in plasmonic gold nanoparticles have been investigated, hot hole lifetimes have not been as thoroughly studied in plasmonic systems. Here, we demonstrate time-resolved emission upconversion microscopy and use it to resolve the lifetime and energy-dependent cooling of d-band holes formed in gold nanoparticles by plasmon excitation and by following plasmon decay into interband and then intraband electron-hole pairs.
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Although photothermal imaging was originally designed to detect individual molecules that do not emit or small nanoparticles that do not scatter, the technique is now being applied to image and spectroscopically characterize larger and more sophisticated nanoparticle structures that scatter light strongly. Extending photothermal measurements into this regime, however, requires revisiting fundamental assumptions made in the interpretation of the signal. Herein, we present a theoretical analysis of the wavelength-resolved photothermal image and its extension to the large particle scattering regime, where we find the photothermal signal to inherit a nonlinear dependence upon pump intensity, together with a contraction of the full-width-at-half-maximum of its point spread function. We further analyze theoretically the extent to which photothermal spectra can be interpreted as an absorption spectrum measure, with deviations between the two becoming more prominent with increasing pump intensities. Companion experiments on individual 10, 20, and 100 nm radius gold nanoparticles evidence the predicted nonlinear pump power dependence and image contraction, verifying the theory and demonstrating new aspects of photothermal imaging relevant to a broader class of targets.
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Nanopartículas Metálicas , Nanopartículas Metálicas/química , Ouro/químicaRESUMO
ConspectusMetal nanoparticles have been utilized for a vast amount of plasmon enhanced spectroscopies and energy conversion devices. Their unique optical properties allow them to be used across the UV-vis-NIR spectrum tuned by their size, shape, and material. In addition to utility in enhanced spectroscopy and energy/charge transfer, the plasmon resonance of metal nanoparticles is sensitive to its surrounding environment in several ways. The local refractive index determines the resonance wavelength, but plasmon damping, as indicated by the homogeneous line width, also depends on the surface properties of the metal nanoparticles. Plasmon oscillations can decay through interband, intraband, radiation, and surface damping. While the first three damping mechanisms can be modeled based on bulk dielectric data using electromagnetic simulations, surface damping does not depend on the material properties of the nanoparticle alone but rather on the interface composition between the nanoparticle and its surrounding environment. In this Account, we will discuss three different metal nanoparticle interfaces, identifying the surface damping contribution from chemical interface damping and how it manifests itself in different interface types. On the way to uncovering the various damping contributions, we use three different single-particle spectroscopic techniques that are essential to measuring homogeneous plasmon line widths: darkfield scattering, photothermal heterodyne imaging, and photoluminescence microscopies. Obtaining the homogeneous plasmon spectrum through single-particle spectroscopy is paramount to measuring changes in plasmon damping, where even minor size and shape heterogeneities can completely obfuscate the broadening caused by surface damping. Using darkfield scattering spectroscopy, we first describe a model for chemical interface damping by expanding upon the surface damping contribution to the plasmon resonance line width to include additional influences due to adsorbed molecules. Based on the understanding of chemical interface damping as a surface damping mechanism, we then carefully compare how two molecular isomers lead to greatly different damping rates upon adsorption to gold nanorods due to differences in the formation of image dipoles within the metal nanoparticles. This plasmon damping dependence on the chemical identity of the interface is strongly correlated with the chemical's electronegativity. A similar damping trend is observed for metal oxide semiconductors, where the metal oxide with greater electron affinity leads to larger interface damping. However, in this case, the mechanism is different for the metal oxide interfaces, as damping occurs through charge transfer into interfacial states. Finally, the damping effect of catalytic metal nanoislands on gold nanorods is compared for the three spectroscopic methods mentioned. Through correlated single-particle scattering, absorption, and photoluminescence spectroscopy, the mechanism for metal-metal interface damping is determined most likely to arise from an enhanced absorption, although charge transfer cannot be ruled out. From this body of research, we conclude that chemical interface damping is a major component of the total damping rate of the plasmon resonance and critically depends on the chemical interface of the metallic nanoparticles. Plasmon damping occurs through distinct mechanisms that are important to differentiate when considering the purpose of the plasmonic nanoparticle: enhanced spectroscopy, energy conversion, or catalysis. It must also be noted that many of the mechanisms are currently indifferentiable, and thus, new single-particle spectroscopic methods are needed to further characterize the mechanisms underlying chemical interface damping.
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Plasmon-induced charge transfer has been studied for the development of plasmonic photodiodes and solar cells. There are two mechanisms by which a plasmonic nanoparticle can transfer charge to an adjacent material: indirect transfer following plasmon decay and direct transfer as a way of plasmon decay. Using single-particle dark-field scattering and photoluminescence imaging and spectroscopy of gold nanorods on various substrates, we identify linewidth broadening and photoluminescence quantum yield quenching as key spectroscopic signatures that are quantitatively related to plasmon-induced interfacial charge transfer. We find that dark-field scattering linewidth broadening is due to chemical interface damping through direct charge injection via plasmon decay. The photoluminescence quantum yield quenching reveals additional mechanistic insight into electron-hole recombination as well as plasmon generation and decay within the gold nanorods. Through these two spectroscopic signatures, we identify charge transfer mechanisms at TiO2 and indium doped tin oxide interfaces and uncover material parameters contributing to plasmon-induced charge transfer efficiency, such as barrier height and resonance energy.
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Plasmonic structures confine electromagnetic energy at the nanoscale, resulting in local, inhomogeneous, controllable heating, but reading out the temperature using optical techniques poses a difficult challenge. Here, we report on the optical thermometry of individual gold nanorod trimers that exhibit multiple wavelength-dependent plasmon modes resulting in measurably different local temperature distributions. Specifically, we demonstrate how photothermal microscopy encodes different wavelength-dependent temperature profiles in the asymmetry of the photothermal image point spread function. These asymmetries are interpreted through companion numerical simulations to reveal how thermal gradients within the trimer can be controlled by exciting its hybridized plasmon modes. We also find that plasmon modes that are optically dark can be excited by focused laser beam illumination, providing another route to modify thermal profiles beyond wide-field illumination. Taken together these findings demonstrate an all-optical thermometry technique to actively create and measure nanoscale thermal gradients below the diffraction limit.
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Nanotubos , Termometria , Diagnóstico por Imagem , Ouro , TemperaturaRESUMO
Single-molecule and super-resolution imaging relies on successful, sensitive, and accurate detection of the emission from fluorescent molecules. Yet, despite the widespread adoption of super-resolution microscopies, single-molecule data processing algorithms can fail to provide accurate measurements of the brightness and position of molecules in the presence of backgrounds that fluctuate significantly over time and space. Thus, samples or experiments that include obscuring backgrounds can severely, or even completely, hinder this process. To date, no general data analysis approach to this problem has been introduced that is capable of removing obscuring backgrounds for a wide variety of experimental modalities. To address this need, we present the Single-Molecule Accurate LocaLization by LocAl Background Subtraction (SMALL-LABS) algorithm, which can be incorporated into existing single-molecule and super-resolution analysis packages to accurately locate and measure the intensity of single molecules, regardless of the shape or brightness of the background. Accurate background subtraction is enabled by separating the foreground from the background based on differences in the temporal variations of the foreground and the background (i.e., fluorophore blinking, bleaching, or moving). We detail the function of SMALL-LABS here, and we validate the SMALL-LABS algorithm on simulated data as well as real data from single-molecule imaging in living cells.
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Imagem Individual de Molécula/métodos , Bacillus subtilis/citologia , Sobrevivência CelularRESUMO
This study focused on the solubility enhancement and the in vivo antidotal efficacy testing of a new potential cyanide (CN) countermeasure, dimethyl trisulfide (DMTS). Various FDA approved cyclodextrins (HPßCD, RMßCD, HPγCD), cosolvents (ethanol, polyethylene glycols, propylene glycol), surfactants (cremophor EL, cremophor RH 40, sodium cholate, sodium deoxycholate, polysorbate 80) and their combinations were applied. Based on the solubility enhancing potential of the tested systems, polysorbate 80 was chosen for further in vivo efficacy studies. A composition comprising 15% polysorbate 80 and 50 mg/ml DMTS with the applied DMTS dose of 100 mg/kg provided a therapeutic antidotal protection of 3.4 × LD50. For comparison, the present therapy of sodium thiosulfate (TS) with the dose of 100 mg/kg provided only 1.1 × LD50 protection, and at the dose of 200 mg/kg, the LD50 was enhanced by 1.3 times. No difference in the therapeutic protection by DMTS was detected when the concentration of polysorbate 80 was increased to 20% (3.2 × LD50 protection). These data demonstrate the potential importance of DMTS as a CN countermeasure, and the formulation comprising polysorbate 80 provides the base of an injectable intramuscular dosage form that can later serve as a CN antidotal kit suitable for mass scenario.
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Antídotos/química , Antídotos/farmacologia , Cianetos/intoxicação , Sulfetos/química , Sulfetos/farmacologia , Animais , Masculino , CamundongosRESUMO
Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue and skin infections and has more recently become prevalent in the community setting as well. Since the use of penicillins to combat S. aureus infections in the 1940s, the bacterium has been notorious for developing resistances to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the persistence of MRSA as well as many other drug resistant bacteria and parasites, there is a growing need to focus on new pharmacological targets. Recently, class II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill this role. Regrettably, scarce biochemical data and no structural data are currently available for the class II FBA found in MRSA (SaFBA). With the recent finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs and its potential for broad spectrum class II FBA inhibition, the lack of information regarding this feature of class IIb FBAs, such as SaFBA, has been limiting for further Z-loop inhibitor development. Therefore, we elucidated the crystal structure of SaFBA to 2.1 Å allowing for a more direct structural analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA's substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition studies for an inhibitor that takes advantage of the Z-loop's flexibility. Together the data offers insight into a class IIb FBA from a pervasively drug resistant bacterium and a comparison of Z-loops and other features between the different subtypes of class II FBAs.
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Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Frutose-Bifosfato Aldolase/química , Frutose-Bifosfato Aldolase/metabolismo , Staphylococcus aureus Resistente à Meticilina/enzimologia , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Domínio Catalítico , Cristalografia por Raios X , Frutose-Bifosfato Aldolase/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade por SubstratoRESUMO
BACKGROUND: Nociceptive pain is required for healthy function, yet, neuropathic pain (disease or injury) can be severely debilitating. Though a wide-array of treatment options are available, they are often systemic and/or invasive. As a promising neuromodulation treatment, Focused ultrasound (FUS) is a noninvasive and highly spatially-targeted technique shown to stimulate neural activity, yet, effects on pain signaling are currently unknown. OBJECTIVE: Develop and validate a method for studying FUS nerve stimulation modulation of pain-evoked neural responses in vivo. METHODS: We developed a high-resolution functional ultrasound (fUS) method capable of mapping cortical responses in healthy and neuropathic pain mice in response to FUS neuromodulation treatment. RESULTS: FUS-evoked hemodynamic responses are correlated with the intensity of peripheral neuromodulation. We confirm functional connectivity is altered in neuropathic mice and demonstrate that FUS can modulate neuropathic pain-evoked hemodynamics. CONCLUSIONS: The findings presented herein provides evidence for an FUS-based nerve pain method and validates the fUS technique developed for monitoring pain-evoked hemodynamics. SIGNIFICANCE: We anticipate that the findings presented herein describe a noninvasive and flexible nerve modulation technique for pain mitigation, furthering evidence for clinical translation.
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Neuralgia , Animais , Neuralgia/terapia , Neuralgia/diagnóstico por imagem , Neuralgia/fisiopatologia , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Mapeamento Encefálico/métodos , Terapia por Ultrassom/métodos , Ultrassonografia/métodosRESUMO
Objective. Linking cavitation and anatomy was found to be important for predictable outcomes in focused-ultrasound blood-brain-barrier-opening and requires high resolution cavitation mapping. However, cavitation mapping techniques for planning and monitoring of therapeutic procedures either (1) do not leverage the full resolution capabilities of ultrasound imaging or (2) place constraints on the length of the therapeutic pulse. This study aimed to develop a high-resolution technique that could resolve vascular anatomy in the cavitation map.Approach. Herein, we develop BandPass-sampled-equivalent-time-active-cavitation-imaging (BP-ETACI), derived from bandpass sampling and dual-frequency contrast imaging at 12.5 MHz to produce cavitation maps prior and during blood-brain barrier opening with long therapeutic bursts using a 1.5 MHz focused transducer in the brain of C57BL/6 mice.Main results. The BP-ETACI cavitation maps were found to correlate with the vascular anatomy in ultrasound localization microscopy vascular maps and in histological sections. Cavitation maps produced from non-blood-brain-barrier disrupting doses showed the same cavitation-bearing vasculature as maps produced over entire blood-brain-barrier opening procedures, allowing use for (1) monitoring focused-ultrasound blood-brain-barrier-opening (FUS-BBBO), but also for (2) therapy planning and target verification.Significance. BP-ETACI is versatile, created high resolution cavitation maps in the mouse brain and is easily translatable to existing FUS-BBBO experiments. As such, it provides a means to further study cavitation phenomena in FUS-BBBO.
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Barreira Hematoencefálica , Microbolhas , Camundongos , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Encéfalo/diagnóstico por imagem , Ultrassonografia , Imageamento por Ressonância Magnética/métodosRESUMO
The lack of a detailed mechanistic understanding for plasmon-mediated charge transfer at metal-semiconductor interfaces severely limits the design of efficient photovoltaic and photocatalytic devices. A major remaining question is the relative contribution from indirect transfer of hot electrons generated by plasmon decay in the metal to the semiconductor compared to direct metal-to-semiconductor interfacial charge transfer. Here, we demonstrate an overall electron transfer efficiency of 44 ± 3% from gold nanorods to titanium oxide shells when excited on resonance. We prove that half of it originates from direct interfacial charge transfer mediated specifically by exciting the plasmon. We are able to distinguish between direct and indirect pathways through multimodal frequency-resolved approach measuring the homogeneous plasmon linewidth by single-particle scattering spectroscopy and time-resolved transient absorption spectroscopy with variable pump wavelengths. Our results signify that the direct plasmon-induced charge transfer pathway is a promising way to improve hot carrier extraction efficiency by circumventing metal intrinsic decay that results mainly in nonspecific heating.
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Focused ultrasound (FUS) peripheral neuromodulation has been linked to nerve displacement caused by the acoustic radiation force; however, the roles of cavitation and temperature accumulation on nerve modulation are less clear, as are the relationships between these three mechanisms of action. Temperature directly changes tissue stiffness and viscosity. Viscoelastic properties have been shown to affect cavitation thresholds in both theoretical and ex vivo models, but the direct effect of temperature on cavitation has not been investigated in vivo. Here, cavitation and tissue displacement were simultaneously mapped in response to baseline tissue temperatures of either 30 °C or 38 °C during sciatic nerve sonication in mice. In each mouse, the sciatic nerve was repeatedly sonicated at 1.1-MHz, 4-MPa peak-negative pressure, 5-ms pulse duration, and either 15- or 30-Hz pulse repetition frequency (PRF) for 10 s at each tissue temperature. Cavitation increased by 1.8-4.5 dB at a tissue temperature of 38 °C compared to 30 °C, as measured both by passive cavitation images and cavitation doses. Tissue displacement also increased by 1.3- [Formula: see text] at baseline temperatures of 38 °C compared to 30 °C. Histological findings indicated small increases in red blood cell extravasation in the 38 °C baseline temperature condition compared to 30 °C at both PRFs. A strong positive correlation was found between the inertial cavitation dose and displacement imaging noise, indicating the potential ability of displacement imaging to simultaneously detect inertial cavitation in vivo. Overall, tissue temperature was found to modulate both in vivo cavitation and tissue displacement, and thus, both tissue temperature and cavitation can be monitored during FUS to ensure both safety and efficiency.
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Sonicação , Camundongos , Animais , TemperaturaRESUMO
According to the Centers for Disease Control and Prevention, hip and femoral neck fractures are common fractures seen in older adults. Lower extremity nerve blocks are a tool available for pain control in these patients. One type of block that can be used in this type of fracture is the fascia iliaca compartment block. Clinicians sometimes do not utilize these blocks despite having been shown to produce better pain relief than a standard regimen of intravenous medications. We present a case of a 76-year-old female patient who had inadequate pain relief from intravenous medications. We illustrate the utilization of a standardized approach to a fascia iliaca compartment block using point-of-care ultrasound in the setting of a femoral neck fracture.
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Plasmonic photocatalysis has attracted interest for its potential to generate energy-efficient reactions, but ultrafast internal conversion limits efficient plasmon-based chemistry. Resonance energy transfer (RET) to surface adsorbates offers a way to outcompete internal conversion pathways and also eliminate the need for sacrificial counter-reactions. Herein, we demonstrate RET between methylene blue (MB) and gold nanorods (AuNRs) using in situ single-particle spectroelectrochemistry. During electrochemically driven reversible redox reactions between MB and leucomethylene blue (LMB), we show that the homogeneous line width is broadened when spectral overlap between AuNR scattering and absorption of MB is maximized, indicating RET. Additionally, electrochemical oxidative oligomerization of MB allowed additional dipole coupling to generate RET at lower energies. Time-dependent density functional theory-based simulated absorption provided theoretical insight into the optical properties, as MB molecules were electrochemically oligomerized. Our findings show a mechanism for driving efficient plasmon-assisted processes by RET through the change in the chemical states of surface adsorbates.
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Imaging applications tailored towards ultrasound-based treatment, such as high intensity focused ultrasound (FUS), where higher power ultrasound generates a radiation force for ultrasound elasticity imaging or therapeutics/theranostics, are affected by interference from FUS. The artifact becomes more pronounced with intensity and power. To overcome this limitation, we propose FUS-net, a method that incorporates a CNN-based U-net autoencoder trained end-to-end on 'clean' and 'corrupted' RF data in Tensorflow 2.3 for FUS artifact removal. The network learns the representation of RF data and FUS artifacts in latent space so that the output of corrupted RF input is clean RF data. We find that FUS-net perform 15% better than stacked autoencoders (SAE) on evaluated test datasets. B-mode images beamformed from FUS-net RF shows superior speckle quality and better contrast-to-noise (CNR) than both notch-filtered and adaptive least means squares filtered RF data. Furthermore, FUS-net filtered images had lower errors and higher similarity to clean images collected from unseen scans at all pressure levels. Lastly, FUS-net RF can be used with existing cross-correlation speckle-tracking algorithms to generate displacement maps. FUS-net currently outperforms conventional filtering and SAEs for removing high pressure FUS interference from RF data, and hence may be applicable to all FUS-based imaging and therapeutic methods.
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Algoritmos , Artefatos , Ultrassonografia/métodosRESUMO
Focused ultrasound (FUS)-based viscoelastic imaging techniques using high frame rate (HFR) ultrasound to track tissue displacement can be used for mechanistic monitoring of FUS neuromodulation. However, a majority of techniques avoid imaging during the active push transmit (interleaved or postpush acquisitions) to mitigate ultrasound interference, which leads to missing temporal information of ultrasound effects when FUS is being applied. Furthermore, critical for clinical translation, use of both axial steering and real-time (<1 s) capabilities for optimizing acoustic parameters for tissue engagement are largely missing. In this study, we describe a method of noninterleaved, single Vantage imaging displacement within an active FUS push with simultaneous axial steering and real-time capabilities using a single ultrasound acquisition machine. Results show that the pulse sequence can track micron-sized displacements using frame rates determined by the calculated time-of-flight (TOF), without interleaving the FUS pulses and imaging acquisition. Decimation by 3-7 frames increases signal-to-noise ratio (SNR) by 15.09±7.03 dB. Benchmarking tests of CUDA-optimized code show increase in processing speed of 35- and 300-fold in comparison with MATLAB parallel processing GPU and CPU functions, respectively, and we can estimate displacement from steered push beams ±10 mm from the geometric focus. Preliminary validation of displacement imaging in humans shows that the same driving pressures led to variable nerve engagement, demonstrating important feedback to improve transducer coupling, FUS incident angle, and targeting. Regarding the use of our technique for neuromodulation, we found that FUS altered thermal perception of thermal pain by 0.9643 units of pain ratings in a single trial. Additionally, 5 [Formula: see text] of nerve displacement was shown in on-target versus off-target sonications. The initial feasibility in healthy volunteers warrants further study for potential clinical translation of FUS for pain suppression.
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Nervo Mediano , Transdutores , Humanos , Dor , Sensação , UltrassonografiaRESUMO
Ultrasound attenuation through soft tissues can produce an acoustic radiation force (ARF) and heating. The ARF-induced displacements and temperature evaluations can reveal tissue properties and provide insights into focused ultrasound (FUS) bio-effects. In this study, we describe an interleaving pulse sequence tested in a tissue-mimicking phantom that alternates FUS and plane-wave imaging pulses at a 1 kHz frame rate. The FUS is amplitude modulated, enabling the simultaneous evaluation of tissue-mimicking phantom displacement using harmonic motion imaging (HMI) and temperature rise using thermal strain imaging (TSI). The parameters were varied with a spatial peak temporal average acoustic intensity (I spta ) ranging from 1.5 to 311 W.cm-2, mechanical index (MI) from 0.43 to 4.0, and total energy (E) from 0.24 to 83 J.cm-2. The HMI and TSI processing could estimate displacement and temperature independently for temperatures below 1.80°C and displacements up to ~117 µm (I spta <311 W.cm-2, MI<4.0, and E<83 J.cm-2) indicated by a steady-state tissue-mimicking phantom displacement throughout the sonication and a comparable temperature estimation with simulations in the absence of tissue-mimicking phantom motion. The TSI estimations presented a mean error of ±0.03°C versus thermocouple estimations with a mean error of ±0.24°C. The results presented herein indicate that HMI can operate at diagnostic-temperature levels (i.e., <1°C) even when exceeding diagnostic acoustic intensity levels (720 mW.cm-2 < I spta < 207 W.cm-2). In addition, the combined HMI and TSI can potentially be used for simultaneous evaluation of safety during tissue elasticity imaging as well as FUS mechanism involved in novel ultrasound applications such as ultrasound neuromodulation and tumor ablation.
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There has been increasing interest in wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. Here, we present such an implant that uses a conventional ultrasound imager for wireless powering and data communication and acts as a probe for real-time temperature sensing, including the monitoring of body temperature and temperature changes resulting from therapeutic application of ultrasound. The sub-0.1-mm3, sub-1-nW device, referred to as a mote, achieves aggressive miniaturization through the monolithic integration of a custom low-power temperature sensor chip with a microscale piezoelectric transducer fabricated on top of the chip. The small displaced volume of these motes allows them to be implanted or injected using minimally invasive techniques with improved biocompatibility. We demonstrate their sensing functionality in vivo for an ultrasound neurostimulation procedure in mice. Our motes have the potential to be adapted to the distributed and localized sensing of other clinically relevant physiological parameters.