Tissue-mimicking Phantoms Research Articles

MR electrical properties mapping using vision transformers and canny edge detectors.

We developed a 3D vision transformer-based neural network to reconstruct electrical properties (EP) from magnetic resonance measurements. Our network uses the magnitude of the transmit magnetic field of a birdcage coil, the associated transceive phase, and a Canny edge mask that identifies the object boundaries as inputs to compute the EP maps. We trained our network on a dataset of 10 000 synthetic tissue-mimicking phantoms and fine-tuned it on a dataset of 11 000 realistic head models. We assessed performance in-distribution simulated data and out-of-distribution head models, with and without synthetic lesions. We further evaluated our network in experiments for an inhomogeneous phantom and a volunteer. The conductivity and permittivity maps had an average peak normalized absolute error (PNAE) of 1.3% and 1.7% for the synthetic phantoms, respectively. For the realistic heads, the average PNAE for the conductivity and permittivity was 1.8% and 2.7%, respectively. The location of synthetic lesions was accurately identified, with reconstructed conductivity and permittivity values within 15% and 25% of the ground-truth, respectively. The conductivity and permittivity for the phantom experiment yielded 2.7% and 2.1% average PNAEs with respect to probe-measured values, respectively. The in vivo EP reconstruction truthfully preserved the subject's anatomy with average values over the entire head similar to the expected literature values. We introduced a new learning-based approach for reconstructing EP from MR measurements obtained with a birdcage coil, marking an important step towards the development of clinically-usable in vivo EP reconstruction protocols.

VP-net: an end-to-end deep learning network for elastic wave velocity prediction in human skin in vivo using optical coherence elastography.

Acne vulgaris, one of the most common skin conditions, affects up to 85% of late adolescents, currently no universally accepted assessment system. The biomechanical properties of skin provide valuable information for the assessment and management of skin conditions. Wave-based optical coherence elastography (OCE) quantitatively assesses these properties of tissues by analyzing induced elastic wave velocities. However, velocity estimation methods require significant expertise and lengthy image processing times, limiting the clinical translation of OCE technology. Recent advances in machine learning offer promising solutions to simplify velocity estimation process. In this study, we proposed a novel end-to-end deep-learning model, named velocity prediction network (VP-Net), aiming to accurately predict elastic wave velocity from raw OCE data of in vivo healthy and abnormal human skin. A total of 16,424 raw phase slices from 1% to 5% agar-based tissue-mimicking phantoms, 28,270 slices from in vivo human skin sites including the palm, forearm, back of the hand from 16 participants, and 580 slices of facial closed comedones were acquired to train, validate, and test VP-Net. VP-Net demonstrated highly accurate velocity prediction performance compared to other deep-learning-based methods, as evidenced by small evaluation metrics. Furthermore, VP-Net exhibited low model complexity and parameter requirements, enabling end-to-end velocity prediction from a single raw phase slice in 1.32ms, enhancing processing speed by a factor of ∼100 compared to a conventional wave velocity estimation method. Additionally, we employed gradient-weighted class activation maps to showcase VP-Net's proficiency in discerning wave propagation patterns from raw phase slices. VP-Net predicted wave velocities that were consistent with the ground truth velocities in agar phantom, two age groups (20s and 30s) of multiple human skin sites and closed comedones datasets. This study indicates that VP-Net could rapidly and accurately predict elastic wave velocities related to biomechanical properties of in vivo healthy and abnormal skin, offering potential clinical applications in characterizing skin aging, as well as assessing and managing the treatment of acne vulgaris.

Size-Sorted Superheated Nanodroplets for Dosimetry and Range Verification of Carbon-Ion Radiotherapy.

Nanodroplets have demonstrated potential for the range detection of hadron radiotherapies. Our formulation uses superheated perfluorobutane (C4F10) stabilized by a poly(vinyl-alcohol) shell. High-LET (linear energy transfer) particles vaporize the nanodroplets into echogenic microbubbles. Tailored ultrasound imaging translates the generated echo-contrast into a dose distribution map, enabling beam range retrieval. This work evaluates the response of size-sorted nanodroplets to carbon-ion radiation. We studied how thesize of nanodroplets affects their sensitivity at various beam-doses and energies, as a function of concentration and shell cross-linking. First, we show the physicochemical characterization of size-isolated nanodroplets by differential centrifugation. Then, we report on the irradiations of the nanodroplet samples in tissue-mimicking phantoms. We compared the response of large (≈900 nm) and small (≈400 nm) nanodroplets to different carbon-ions energies and evaluated their dose linearity and concentration detection thresholds by ultrasound imaging. Additionally, we verified the beam range detection accuracy for the nanodroplets samples. All nanodroplets exhibited sensitivity to carbon-ions with high range verification precision. However, smaller nanodroplets required a higher concentration sensitivity threshold. The vaporization yield depends on the carbon-ions energy and dose, which are both related to particle count/spot. These findings confirm the potential of nanodroplets for range detection, with performance depending on nanodroplets' properties and beam parameters.

Feasibility of Monitoring Tissue Properties During Microcirculation Disorder Using a Compact Fiber-Based Probe With Sapphire Tip.

One of the urgent tasks of modern medicine is to detect microcirculation disorder during surgery to avoid possible consequences like tissue hypoxia, ischemia, and necrosis. To address this issue, in this article, we propose a compact probe with sapphire tip and optical sensing based on the principle of spatially resolved diffuse reflectance analysis. It allows for intraoperative measurement of tissue effective attenuation coefficient and its alteration during the changes of tissue condition, caused by microcirculation disorder. The results of experimental studies using (1) a tissue-mimicking phantom based on lipid emulsion and hemoglobin and (2) a model of hindlimb ischemia performed in a rat demonstrated the ability to detect rapid changes of tissue attenuation confirming the feasibility of the probe to sense the stressful exposure. Due to a compact design of the probe, it could be useful for rather wide surgical operations and diagnostic purposes as an auxiliary instrument.

Pulse-Echo Ultrasound for Quantitative Measurements of Two Uncorrelated Elastic Parameters

ObjectiveThis paper describes the relationship between elastic tissue properties and strain and presents an initial investigation of pulse-echo ultrasound to measure two uncorrelated elastic parameters in tissue-mimicking phantoms. The two elastic parameters are the shear modulus, related to deformation of shape, and what we in the paper define as the nonlinear compressibility, related to deformation of volume. MethodsWe prepared tissue-mimicking phantoms containing lesions of variable shear modulus and variable nonlinear compressibility. An in-house framework for shear wave imaging was developed using ultrasound radiation force at 4.5 MHz to induce shear waves and plane wave imaging with pulses in a frequency band centered around 12.5 MHz to track the shear waves. For measurements of nonlinear compressibility, co-propagating dual-frequency pulse complexes at 0.7 MHz and 14 MHz were applied. Algorithms were implemented on a Verasonics Vantage ultrasound scanner and a custom-made multi-frequency ultrasound transducer was used. Mechanical indentation measurements were performed to validate ultrasound measurements of the shear modulus. For the nonlinear compressibility, ultrasound measurements were compared to results derived from the literature. ResultsWe found good agreement in elasticity results from ultrasound measurements and mechanical indentation as well as when comparing with results derived from the literature. ConclusionResults of the current investigation were promising. We plan patient studies involving thyroid lesions and liver steatosis to explore whether measurements of elastic parameters related both to shape deformation and volume deformation are useful in clinical practice.

Non-Invasive Blood-Brain Barrier Disruption Using Acoustic Holography With a Clinical Focused Ultrasound System.

Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a hemispherical 1024-element phased array transducer and explored how it could benefit ultrasound-mediated blood-brain barrier (BBB) disruption. With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each element's phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz transducer being tested clinically to enhance drug delivery via BBB disruption. The holograms were evaluated in a tissue-mimicking phantom and in vivo in experiments disrupting the BBB in rats and in a macaque. We also explored whether this approach could mitigate secondary reflections from the skull using simulations of transcranial focusing in clinical treatments of transcranial sonication for BBB disruption. This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density. Simulations suggest that the method could also mitigate secondary reflections during transcranial sonication.

SELFNet: Denoising Shear Wave Elastography Using Spatial-temporal Fourier Feature Networks

ObjectiveUltrasound-based shear wave elastography offers estimation of tissue stiffness through analysis of the propagation of a shear wave induced by a stimulus. Displacement or velocity fields during the process can contain noise as a result of the limited number of acquisitions. With advances in physics-informed deep learning, neural networks can approximate a physics field by minimizing the residuals of governing physics equations. MethodsIn this research, we introduce a shear wave elastography Fourier feature network (SELFNet) using spatial-temporal random Fourier features within a physics-informed neural network framework to estimate and denoise particle displacement signals. The network uses a sparse mapping to increase robustness and incorporates the governing equations for regularization while simultaneously learning the mapping of the shear modulus. The method was evaluated in datasets from tissue-mimicking phantom of lesions and ex vivo tissue. ResultsThe findings indicate that SELFNet is capable of smoothing out the noise in phantom lesions with different stiffness and sizes, outperforming a reference Gaussian filtering method by 17% in relative ℓ2 error, 45% in reconstruction root-mean-square error. Furthermore, the ablation study suggested that SELFNet can prevent over-fitting through the Fourier feature mapping module. An ex vivo study confirmed its applicability to different types of tissue. ConclusionThe implementation of SELFNet shows promise for shear wave elastography with limited acquisitions. In this context, subject to successful translation, it has the potential to be extended to clinical applications, such as the diagnosis of cancer or liver disease.

High-Intensity focused ultrasound linear array and system for dermatology treatment

Dermatological lesions are typically located just a few millimeters below the surface of the skin, which constrains the efficacy of optical-based therapeutic methods such as photothermal and photodynamic therapy due to limited therapeutic depth caused by optical scattering. As an alternative, high-intensity focused ultrasound (HIFU) has been explored for its potential to treat a variety of dermatological conditions because it offers greater flexibility in terms of treatment depth. Since dermatological lesions have a small thickness ranging from 1.5 to 2.0 mm, high-frequency ultrasound (3–10 MHz or higher) is preferred as the focal area is proportional to the operating frequency. However, due to the difficulty in fabricating HIFU array transducers at this frequency range, the majority of HIFU treatments for dermatology rely on single element transducers. Despite the advantages of HIFU, single-element-based HIFU systems are limited in prevalent use for dermatology treatment due to their fixed focal length and mechanical movement for treatment, which can be time-consuming and unsuitable for treating multiple lesions. To address this, we present a newly developed HIFU linear array and 128-channel driving electronics specifically designed for dermatology treatment. This array consists of 128 elements, has a center frequency of 3.7 MHz, an elevation focal length of 28 mm, and an F-number of 1.27 in the elevation direction. The array has a footprint of 71.6 mm by 22 mm. Experiments using a tissue-mimicking phantom have demonstrated that the HIFU linear array and system are capable of transmitting sufficient ultrasound energy to create coagulation inside the phantom.

Cubic nonlinearity and surface shock waves in soft tissue-like materials

The cubic nonlinearity of shear wave propagation plays a significant role in brain injury biomechanics. However, soft materials, like the brain, also support the propagation of surface waves, which produce a combination of longitudinal and transverse deformation. The order of the nonlinearity of surface waves in soft materials is still unknown. Here, we directly observe nonlinear Scholte waves propagating in an interface formed by an incompressible gelatin tissue-mimicking phantom and a water layer using ultrasound imaging operated as fast as 16667 frames per second. A two-dimensional correlation-based tracking algorithm was utilized to extract movies of the movement produced by the surface wave. Our results show that the initially nearly monochromatic wave becomes progressively distorted with the propagation due to nonlinearity. The distortion of the wave and its frequency spectrum indicate a high content of odd harmonics when compared with even harmonics. Additionally, by fitting our experimental data to a minimalist one-dimensional model based on the wave speed variation as a function of the perturbation amplitude, we found a cubic nonlinear parameter 46 times larger than the quadratic nonlinear parameter. Overall, the wave distortion, the harmonic development, and the dependence of the wave speed with the amplitude prove that cubic nonlinearity is essential to modeling nonlinear Scholte wave propagation.

Enabling Visible Light Sensitization of YbIII, NdIII and ErIII in Dimeric LnIII/GaIII Metallacrowns through Functionalization with RuII Complexes for NIR-II Multiplex Imaging.

Multiplex imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides exciting opportunities for more precise understanding of biological processes and more accurate diagnosis of diseases by enabling real-time acquisition of images with improved contrast and spatial resolution in deeper tissues. Today, the number of imaging agents suitable for this modality remains very scarce. In this work, we have synthesized and fully characterized, including theoretical calculations, a series of dimeric LnIII/GaIII metallacrowns bearing RuII polypyridyl complexes, LnRu-3 (Ln = YIII, YbIII, NdIII, ErIII). Relaxed structures of YRu-3 in the ground and the excited electronic states have been calculated using dispersion-corrected density functional theory methods. Detailed photophysical studies of LnRu-3 have demonstrated that characteristic emission signals of YbIII, NdIII and ErIII in the NIR-II range can be sensitized upon excitation in the visible range through RuII-centered metal-to-ligand charge transfer (MLCT) states. We have also showed that these NIR-II signals are unambiguously detected in an imaging experiment using capillaries and biological tissue-mimicking phantoms. This work opens unprecedented perspectives for NIR-II multiplex imaging using LnIII-based molecular compounds.

Assessment of thermochromic phantoms for characterizing microwave ablation devices.

Thermochromic gel phantoms provide a controlled medium for visual assessment of thermal ablation device performance. However, there are limited studies reporting on the comparative assessment of ablation profiles assessed in thermochromic gel phantoms against those in ex vivo tissue. The objective of this study was to compare microwave ablation zones in a thermochromic tissue-mimicking gel phantom and ex vivo bovine liver and to report on measurements of the temperature-dependent dielectric and thermal properties of the phantom. Thermochromic polyacrylamide phantoms were fabricated following a previously reported protocol. Phantom samples were heated to temperatures in the range of 20°C-90°C in a temperature-controlled water bath, and colorimetric analysis of images of the phantom taken after heating was used to develop a calibration between color changes and the temperature to which the phantom was heated. Using a custom, 2.45GHz water-cooled microwave ablation antenna, ablations were performed in fresh ex vivo liver and phantoms using 65W applied for 5min or 10min (n=3 samples in each medium for each power/time combination). Broadband (500MHz-6GHz) temperature-dependent dielectric and thermal properties of the phantom were measured over the temperature range of 22°C-100°C. Colorimetric analysis showed that the sharp change in gel phantom color commences at a temperature of 57°C. Short and long axes of the ablation zone in the phantom (as assessed by the 57°C isotherm) for 65W, 5min ablations were aligned with the extents of the ablation zone observed in ex vivo bovine liver. However, for the 65W, 10min setting, ablations in the phantom were on average 23.7% smaller in the short axis and 7.4 % smaller in the long axis than those observed in ex vivo liver. Measurements of the temperature-dependent relative permittivity, thermal conductivity, and volumetric heat capacity of the phantom largely followed similar trends to published values for ex vivo liver tissue. Thermochromic tissue-mimicking phantoms provides a controlled, and reproducible medium for comparative assessment of microwave ablation devices and energy delivery settings. However, ablation zone size and shapes in the thermochromic phantom do not accurately represent ablation sizes and shapes observed in ex vivoliver tissue for high energy delivery treatments (65W, 10min). One cause for this limitation is the difference in temperature-dependent thermal and dielectric properties of the thermochromic phantom compared to ex vivobovine liver tissue, as reported in the present study.

Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0–37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70–150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.

Depth detection limit of a fluorescent object in tissue-like medium with background emission in continuous-wave measurements: a phantom study.

Although the depth detection limit of fluorescence objects in tissue has been studied, reports with a model including noise statistics for designing the optimum measurement configuration are missing. We demonstrate a variance analysis of the depth detection limit toward clinical applications such as noninvasively assessing the risk of aspiration. It is essential to analyze how the depth detection limit of the fluorescence object in a strong scattering medium depends on the measurement configuration to optimize the configuration. We aim to evaluate the depth detection limit from theoretical analysis and phantom experiments and discuss the source-detector distance that maximizes this limit. Experiments for detecting a fluorescent object in a biological tissue-mimicking phantom of ground beef with background emission were conducted using continuous wave fluorescence measurements with a point source-detector scheme. The results were analyzed using a model based on the photon diffusion equations. Then, variance analysis of the signal fluctuation was introduced. The model explained the measured fluorescence intensities and their fluctuations well. The variance analysis showed that the depth detection limit in the presence of ambient light increased with the decrease in the source-detector distance, and the optimum distance was in the range of 10 to 15mm. The depth detection limit was found to be with this optimum distance for the phantom. The presented analysis provides a guide for the optimum design of the measurement configuration for detecting fluorescence objects in clinical applications.

ISM band CPW-fed antenna for detection of skin cancer

A CPW-fed antenna sensor with high quality factor is designed to identify the skin cancer. The proposed antenna operates in the ISM band at 2.47 GHz frequency. The proposed antenna aims to exploit the variations in dielectric constants of skin, fat, and muscle tissues to enable non-invasive and early detection of skin cancer. The antenna design process involves considerations for achieving a high frequency shift and quality factor to discern subtle variations in dielectric properties. Electromagnetic simulations, utilizing advanced numerical techniques are employed to analyze the antenna's performance in different tissue environments. The proposed antenna design is optimized for enhancing its sensitivity to changes in the dielectric constants associated with healthy and cancerous skin tissues. To validate the antenna's effectiveness, experimental setups using tissue-mimicking phantoms are utilized. This research not only emphasizes the technical aspects of antenna design but also underscores the potential clinical applications for non-invasive skin cancer detection.

Multimodal optical ultrasound imaging: Real-time imaging under concurrent CT or MRI

Optical ultrasound (OpUS) imaging is an ultrasound modality that utilizes fiber-optic ultrasound sources and detectors to perform pulse-echo ultrasound imaging. These probes can be constructed entirely from glass optical fibers and plastic components, and as such, these devices have been predicted to be compatible with computed tomography (CT) and magnetic resonance imaging (MRI), modalities that use intense electromagnetic fields for imaging. However, to date, this compatibility has not been demonstrated. In this work, a free-hand OpUS imaging system was developed specifically to investigate the compatibility of OpUS systems with CT and MRI imaging systems. The OpUS imaging platform discussed in this work was used to perform real-time OpUS imaging under (separately) concurrent CT and MRI. CT and MRI imaging of the OpUS probe was used to determine if the probe itself would induce artifacts in the CT and MRI imaging, and ultrasound resolution targets and background measurements were used to assess any impact of CT and MRI on the OpUS signal fidelity. These measurements demonstrate that there was negligible interaction between the OpUS system and both the CT and MRI systems, and to further demonstrate this capability, concurrent OpUS-CT and OpUS-MRI imaging was conducted of a tissue-mimicking phantom and a dynamic motion phantom. This work presents a comprehensive demonstration of an OpUS imaging system operating alongside CT and MRI, which opens up new applications of ultrasound imaging in electromagnetically challenging settings.

Circuit modelling and validating a capacitively loaded implantable antenna with its sensitivity analysis for biomedical applications

This paper presents a flexible and capacitively loaded implantable antenna with its sensitivity analysis for biomedical applications. The proposed antenna is designed to operate within the ISM (Industrial, Scientific, and Medical) band, which ranges from 2.4 to 2.48 GHz. The overall dimensions of an antenna are 8 × 8 × 0.25 mm3. The substrate material FR-4 is utilised with a dielectric constant (ε r) 4.4, loss tangent (δ) 0.0022 and a thickness of 0.25 mm for the proposed antenna. An ultra-flexible superstrate material, Parylene C, is used with a thickness of 40 microns on both sides of an antenna to avoid direct contact of metallization with human tissue. Further, the proposed antenna is initially implanted inside a four-layer cubic (FLC) phantom, and then its parameters are validated using the CST Hugo voxel model. The simulated bandwidth of an antenna is 28.16 %, whereas measured bandwidths are 32.25 % inside the tissue-mimicking phantom and 64 % inside minced pork. Moreover, assessing the specific absorption rate (SAR) in a realistic model ensures patient safety by following the guidelines outlined in C95.1–1999 for 1g and 10g of tissue. The simulated and measured results are in close agreement, making the designed antenna appropriate for biomedical applications.

NIR-II femtosecond laser-induced nonlinear absorption facilitates foreground-extraction photoacoustic imaging by monolayer WS2-PVP nanosheets

Exogenous contrast agents have been extensively applied in photoacoustic (PA) molecular imaging for disease diagnosis, benefiting from their advantageous optical, thermal, and internal delivery properties. However, their in vivo performance was inevitably interfered by background tissue optical absorption, resulting in low imaging contrast and sensitivity. Here, we report a NIR-II femtosecond laser-induced nonlinearly enhanced PA imaging technique based on two-photon absorption of monolayer WS2-PVP nanosheets (NSs), which facilitates foreground extraction of the targeting region with the background signal being significantly suppressed. The optical nonlinearity of the monolayer WS2-PVP NSs was first demonstrated by a Z-scan system under the irradiation of a femtosecond laser to be 0.38, with an antithesis of virtually zero for the tissue-mimicking sample. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that the nonlinear PA enhancement of monolayer WS2-PVP NSs can facilitate foreground-extraction imaging at deep-seated position up to 4 mm. In addition, the in vivo foreground-extraction imaging ability by using monolayer WS2-PVP NSs was further demonstrated by mouse tumor models, where the tumor regions were specifically extracted with high imaging contrast. This work proposed a nonlinearly enhanced contrast mechanism of PA nanoprobes, prefiguring great potential for high-contrast and high-specificity PA molecular imaging.

Fabrication and Characterization of Brain Tissue Phantoms Using Agarose Gels for Ultraviolet Vision Systems.

Recreating cerebral tissue using a tissue-mimicking phantom is valuable because it provides a tool for studying physiological and biological processes related to tissues without the necessity of performing the study directly in the tissue or even in a patient. The reproduction of the optical properties allows investigation in areas such as imaging, optics, and ultrasound, among others. This paper presents a methodology for manufacturing agarose-based phantoms that mimic the optical characteristics of brain tissue using scattering and absorbing agents and proposes combinations of these agents to recreate the healthy brain tissue optical coefficients within the wavelength range of 350 to 500 nm. The results of the characterization of the manufactured phantoms propose ideal combinations of the used materials for their use in controlled environment experiments in the UV range, following a cost-effective methodology.

Chemigenetic Far-Red Labels and Ca2+ Indicators Optimized for Photoacoustic Imaging.

Photoacoustic imaging is an emerging modality with significant promise for biomedical applications such as neuroimaging, owing to its capability to capture large fields of view deep inside complex scattering tissue. However, widespread adoption of this technique has been hindered by a lack of suitable molecular reporters for this modality. In this work, we introduce chemigenetic labels and calcium sensors specifically tailored for photoacoustic imaging, using a combination of synthetic dyes and HaloTag-based self-labeling proteins. We rationally design and engineer far-red "acoustogenic" dyes, showing high photoacoustic turn-ons upon binding to HaloTag, and develop a suite of tunable calcium indicators based on these scaffolds. These first-generation photoacoustic reporters show excellent performance in tissue-mimicking phantoms, with the best variants outperforming existing sensors in terms of signal intensity, sensitivity, and photostability. We demonstrate the application of these ligands for labeling HaloTag-expressing neurons in mouse brain tissue, producing strong, specifically targeted photoacoustic signal, and provide a first example of in vivo labeling with these chemigenetic photoacoustic probes. Together, this work establishes a new approach for the design of photoacoustic reporters, paving the way toward deep tissue functional imaging.

Acoustomotive diffuse correlation spectroscopy for sensing mechanical stiffness in tissue-mimicking phantoms.

Many diseases, such as inflammation, dropsy, or tumors, often cause alterations in the mechanical stiffness of human tissues. Ultrasound-based techniques are commonly adopted in clinics for stiffness assessment, whereas optical methodologies hold promise for sensing strain changes and providing optical information pertaining to the microcirculatory network, thereby facilitating comprehensive measurements of tissue physiopathology. Diffuse correlation spectroscopy (DCS), an emerging dynamic light scattering technique, has been used to capture the enhanced motion of light scatterers induced by acoustic radiation force (ARF). Theoretically, the amplitude of this enhanced scatterers motion is related to the medium stiffness. Based on this relationship, we report a light coherent technique that combines ARF and DCS to qualitatively evaluate changes in the stiffness of medium. We experimentally demonstrate the accuracy and feasibility of this technique for probing stiffness in homogeneous phantom by comparing it with independent ultrasound methods. Additionally, we explore a potential application of this technique in distinguishing between fluid filled lesion and homogeneous tissue through heterogeneous phantom experiments. This unique combination of ARF and DCS, namely, acoustomotive DCS (AM-DCS), would provide an alternative way to measure particle-motion related stiffness, thereby assisting in the diagnosis and treatment of diseases.