Acoustic Radiation Force Research Articles

Systematic quantification of differences in shear wave elastography estimates between linear-elastic and viscoelastic material assumptionsa).

Quantitative, accurate, and standardized metrics are important for reliable shear wave elastography (SWE)-based biomarkers. For over two decades, the linear-elastic material assumption has been employed in SWE modes. In recent years, viscoelasticity estimation methods have been adopted in a few clinical systems. The current study aims to systematically quantify differences in SWE estimates obtained using linear-elastic and viscoelastic material assumptions. An acousto-mechanical simulation framework of acoustic radiation force impulse-based SWE was created to elucidate the effect of material viscosity and shear modulus on SWE estimates. Shear modulus estimates exhibited errors up to 72% when a numerical viscoelastic phantom was assessed as linearly elastic. Shear modulus estimates of polyvinyl alcohol phantoms between rheometry and SWE following the Kelvin-Voigt viscoelastic model assumptions were not significantly different. However, the percentage difference in shear modulus estimates between rheometry and SWE using the linear-elastic assumption was 50.1%-62.1%. In ex vivo liver, the percentage difference in shear modulus estimates between linear-elastic and viscoelastic methods was 76.1%. These findings provide a direct and systematic quantification of the potential error introduced when viscoelastic tissues are imaged with SWE following the linear-elastic assumption. This work emphasizes the need to utilize viscoelasticity estimation methods for developing robust quantitative imaging biomarkers.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.Methods: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histological methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.Results: Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

A Microchannel Device for Droplet Classification by Manipulation Using Piezoelectric Vibrator

Emulsion formulations should be monodispersed in terms of their stability. Therefore, there is a need for a device that can classify droplets of the desired size from polydispersed emulsions in a fluidized bed manufacturing system. In the previous study, we evaluated the fabrication of a droplet manipulation device using acoustic radiation forces through simulation using the finite element method. In this study, particle manipulation experiments using 1, 6, and 10 µm polystyrene particles were first estimated and evaluated in comparison with their theoretical particle behavior. Based on the results we obtained, the driving conditions and droplet behavior were derived, and the droplet manipulation device using ultrasonic waves to shrink monodisperse emulsions was evaluated. As a result, the droplet classification effect in the microchannel was confirmed to be consistent with the droplet behavior prediction, and the microchannel structure with a constriction component improved its classification effect.

In Vivo Evaluation of Corneal Biomechanics Following Cross-Linking Surgeries Using Optical Coherence Elastography in a Rabbit Model of Keratoconus.

Validation of the feasibility of novel acoustic radiation force optical coherence elastography (ARF-OCE) for the evaluation of biomechanical enhancement of the in vivo model of keratoconus by clinical cross-linking (CXL) surgery. Twelve in vivo rabbit corneas were randomly divided into two groups. Both groups were treated with collagenase type II, and a keratoconus model was obtained. Then, the two groups were treated with CXL procedures with different irradiation energy of 15 J and 30 J (CXL-15 J and CXL-30 J, respectively). An ARF-OCE probe with an ultrasmall ultrasound transducer was used to detect the biomechanical properties of cornea. An antisymmetric Lamb wave model was combined with the frequency dispersion relationship to achieve depth-resolved elastography. Compared with the phase velocity of the Lamb wave in healthy corneas (approximately 3.96 ± 0.27 m/s), the phase velocity of the Lamb wave was lower in the keratoconus region (P < 0.05), with an average value of 3.12 ± 0.12 m/s. Moreover, the corneal stiffness increased after CXL treatment (P < 0.05), and the average phase velocity of the Lamb wave was 4.3 ± 0.19 m/s and 4.54 ± 0.13 m/s after CXL-15 J and CXL-30 J treatment. The Young's moduli of the keratoconus regions were significantly lower than the healthy corneas. Moreover, the Young's modulus of the keratoconus regions was significantly higher after CXL-30 J treatment than after CXL-15 J treatment. We demonstrated that the ARF-OCE technique has great potential in screening keratoconus and guiding clinical CXL treatment. This work accelerates the clinical translation of OCE systems using ultrasmall ultrasound transducers and is used to guide CXL procedures.

Point-shear wave elastography generated by acoustic radiation force impulse in chronic pancreatitis.

Transcutaneous point-shear wave elastography (p-SWE) performed using an acoustic radiation force impulse can be used to quantify pancreatic stiffness in chronic pancreatitis (CP). We aimed to evaluate its usefulness to diagnose and monitor CP. 175 participants were included in this prospective study including patients with CP (n=65), liver cirrhosis (LC; n=60), alcohol abuse (n=10) and healthy controls (n=40). Point-shear wave elastography of the pancreas was performed and quantified as median shear wave velocity (SWV). In the same way, p-SWE of the spleen served as a marker of portal hypertension. The M-ANNHEIM Severity score was used as global marker for disease activity in CP. Compared to healthy controls, pancreatic SWV was significantly elevated in CP (1.38 vs. 0.96m/s; p<0.0001, MWU-test). Pancreatic SWV was increased in alcoholic CP but not in hereditary CP. Receiver operating characteristic analysis revealed 1.2m/s as the optimal cut-off to identify non-heredity-CP subjects (90% specificity; 81% sensitivity; 92% positive predictive value). Pancreatic SWV correlated significantly with the M-ANNHEIM Severity score, severity of CP-typical complications (both p<0.05, linear regression analysis), morphological changes of the pancreas and need for hospital treatment (both p<0.05, MWU-test) but not with exocrine or endocrine insufficiency. Pancreatic SWV >1.7m/s was identified to predict M-ANNHEIM Severity score ≥11 points. Pancreatic SWV was also elevated in LC (1.42m/s; p<0.001), correlating with increased splenic SWV. Transcutaneous pancreatic p-SWE represents a bedside, cost-effective and non-invasive tool which adds valuable information to the process of diagnosing and monitoring CP. By portal hypertension, an increased pancreatic SWV must be expected.

Three-dimensional array of microbubbles sonoporation of cells in microfluidics.

Sonoporation is a popular membrane disruption technique widely applicable in various fields, including cell therapy, drug delivery, and biomanufacturing. In recent years, there has been significant progress in achieving controlled, high-viability, and high-efficiency cell sonoporation in microfluidics. If the microchannels are too small, especially when scaled down to the cellular level, it still remains a challenge to overcome microchannel clogging, and low throughput. Here, we presented a microfluidic device capable of modulating membrane permeability through oscillating three-dimensional array of microbubbles. Simulations were performed to analyze the effective range of action of the oscillating microbubbles to obtain the optimal microchannel size. Utilizing a high-precision light curing 3D printer to fabricate uniformly sized microstructures in a one-step on both the side walls and the top surface for the generation of microbubbles. These microbubbles oscillated with nearly identical amplitudes and frequencies, ensuring efficient and stable sonoporation within the system. Cells were captured and trapped on the bubble surface by the acoustic streaming and secondary acoustic radiation forces induced by the oscillating microbubbles. At a driving voltage of 30 Vpp, the sonoporation efficiency of cells reached 93.9% ± 2.4%.

Comparisons of the acoustic radiation force of ultrasonic standing waves in half-wavelength and quarter-wavelength micro-resonators of cylindrical geometry

Ultrasonic standing waves with specific wavelengths generated in the multi-layered micro-resonators were numerically and experimentally analyzed. Using a three-dimensional scanning fluorescence microscope, the acoustophoretic motion of fluorescent microparticles within the micro-resonators was carefully and accurately measured. The manufactured micro-resonators were validated by comparing the location of the acoustic pressure nodal plane and the average energy density curves derived from numerical and experimental results. Results confirmed that the acoustic radiation force of the induced ultrasonic standing waves drives the microparticles vertically within the micro-resonators and their average energy density increases as the sinusoidal voltage applied to the piezoelectric transducer increases. Semi-empirical correlations were developed for the average energy density, based on experimental results for a wide range of the applied voltage amplitudes. The correlations were in good agreement, within less than 20 % of the experimental values measured for both the half-wavelength and quarter-wavelength micro-resonators.

Wearable bioadhesive ultrasound shear wave elastography.

Acute liver failure (ALF) is a critical medical condition defined as the rapid development of hepatic dysfunction. Conventional ultrasound elastography cannot continuously monitor liver stiffness over the course of rapidly changing diseases for early detection due to the requirement of a handheld probe. In this study, we introduce wearable bioadhesive ultrasound elastography (BAUS-E), which can generate acoustic radiation force impulse (ARFI) to induce shear waves for the continuous monitoring of modulus changes. BAUS-E contains 128 channels with a compact design with only 24 mm in the azimuth direction for comfortable wearability. We further used BAUS-E to continuously monitor the stiffness of in vivo rat livers with ALF induced by d-galactosamine over 48 hours, and the stiffness change was observed within the first 6 hours. BAUS-E holds promise for clinical applications, particularly in patients after organ transplantation or postoperative care in the intensive care unit (ICU).

Feasibility of Phase Velocity Imaging Using Multi Frequency Oscillation-Shear Wave Elastography.

To assess viscoelasticity, a pathologically relevant biomarker, shear wave elastography (SWE) generally uses phase velocity (PV) dispersion relationship generated via pulsed acoustic radiation force (ARF) excitation pulse. In this study, a multi-frequency oscillation (MFO)- excitation pulse with higher weight to higher frequencies is proposed to generate PV images via the generation of motion with energy concentrated at the target frequencies in contrast to the broadband frequency motion generated in pulsed SWE (PSWE). The feasibility of MFO-SWE to generate PV images at 100 to 1000 Hz in steps of 100 Hz was investigated by imaging 6 and 70 kPa inclusions with 6.5 and 10.4 mm diameter and ex vivo bovine liver with and without the presence of an aberration layer and chicken muscle ex vivo, and 4T1 mouse breast tumor, in vivo with comparisons to PSWE. MFO-SWE-derived CNR was statistically higher than PSWE for 6 kPa (both with and without aberration) and 70 kPa (with aberration) inclusions and derived SNR of the liver was statistically higher than PSWE at higher frequency (600-1000 Hz). Quantitatively, at 600-1000 Hz, MFO-SWE improved CNR of inclusions (without and with) aberration on an average by (8.2 and 156)% and of the tumor by 122%, respectively, and improved SNR of the liver (without and with) aberration by (20.2 and 51.5)% and of chicken muscle by 72%, respectively compared to the PSWE. These results indicate the advantages of MFO-SWE to improve PV estimation at higher frequencies which could improve viscoelasticity quantification and feature delineation.

Investigation on submicron particle separation and deflection using tilted-angle standing surface acoustic wave microfluidics

With the development of in vitro diagnostics, extracting submicron scale particles from mixed body fluids samples is crucial. In recent years, microfluidic separation has attracted much attention due to its high efficiency, label-free, and inexpensive nature. Among the microfluidic-based separation, the separation based on ultrasonic standing waves has gradually become a powerful tool. A microfluid environment containing a tilted-angle ultrasonic standing surface acoustic wave (taSSAW) field has been widely adapted and designed to separate submicron particles for biochemical applications. This paper investigated submicron particle defection in microfluidics using taSSAWs analytically. Particles with 0.1–1 μm diameters were analyzed under acoustic pressure, flow rate, tilted angle, and SSAW frequency. According to different acoustic radiation forces acting on the particles, the motion of large-diameter particles was more likely to deflect to the direction of the nodal lines. Decreasing the input flow rate or increasing acoustic pressure and acoustic wave frequency can improve particle deflection. The tilted angle can be optimized by analyzing the simulation results. Based on the simulation analysis, we experimentally showed the separation of polystyrene microspheres (100 nm) from the mixed particles and exosomes (30–150 nm) from human plasma. This research results can provide a certain reference for the practical design of bioparticle separation utilizing acoustofluidic devices.

Ultrasound-based quantitative tools in predicting renal involvement in asymptomatic primary hyperparathyroidism

PurposeAsymptomatic primary hyperparathyroidism (aPHPT) has been recognized as a condition that can lead to renal complications. Timely identification of prognostic indicators for renal impairment holds the potential to facilitate proactive monitoring and treatment strategies in these patients. This study aims to investigate the utility of acoustic radiation force impulse (ARFI) imaging and renal resistive index (RRI), in identifying renal parenchymal and vascular changes in patients with aPHPT.MethodsForty-two patients with aPHPT and 42 controls matched for age, sex, and body mass index were included in the study. The presence of renovascular changes was evaluated by RRI measurement with Doppler ultrasonography, and the presence of renal parenchymal involvement was evaluated by ARFI quantification, given as shear wave velocity (SWV).ResultsIn aPHPT patients, both the mean RRI and mean SWV values exhibited substantial elevation compared to the control group (P < 0.001 for both). Significant associations were observed between SWV values and serum calcium, parathyroid hormone (PTH), and adenoma size within the patient group (P < 0.001, P < 0.001, P = 0.016, respectively). Similarly, the mean RRI demonstrated positive correlations with serum calcium and PTH levels in the patient group (P< 0.001, P = 0.011, respectively). Multivariate linear regression analysis underscored the connection between mean RRI and mean SWV values with serum calcium levels within the patient group. In addition, serum PTH levels affected mean SWV positively and significantly.ConclusionThe use of ARFI imaging and RRI measurements appears to hold potential in identifying renal involvement in patients with aPHPT.

Our experience with liver and spleen elastography in the prediction of oesophageal varices.

Variceal bleeding is an important cause of mortality in patients with chronic liver disease (CLD). The gold standard for detection and grading of oesophageal varices (EV) is upper gastrointestinal endoscopy. However, it is expensive, time-consuming and invasive. This study aimed to find any association between splenic shear wave velocity (SWV) measured by acoustic radiation force imaging (ARFI) and the presence of EV. The quasi-experimental study included 50 patients with CLD and 50 subjects without CLD as the control group. Both underwent upper abdominal ultrasonography followed by elastographic assessment on a Siemens Acuson S2000TM ultrasound system. A comparison of the findings was made between the control and patient groups. Both groups had similar hepatic size while patients with CLD had larger splenic size and area (p < 0.05). The CLD patients had higher mean hepatic and splenic SWV compared with the control group (p < 0.05). The mean splenic size and splenic SWV were higher in patients with varices than in those without varices (p < 0.05). Chronic liver disease causes significant increase in liver and splenic stiffness with splenic SWV values being higher for patients with varices emphasising the role of elastography as a non-invasive predictor for the presence of EVs. Splenic SWV had the highest sensitivity and specificity, which was augmented by a combination of hepatic and splenic SWV. Thus, splenic SWV alone or in combination with hepatic SWV is a useful technique for prediction of the presence of EVs. This study aims to find an alternative non-invasive and cost-effective technique for screening of EV.

A fundamental study of flotation separation of mineral particles using ultrasound-induced bubbles

This paper describes the flotation separation of naturally hydrophobic coal particles and hydrophilic quartz particles in water (free of any reagents) using ultrasound-induced bubbles only, without any additional air supply. A laboratory-scale flow tubing system with an ultrasound transducer was designed and used. The experiments were conducted for coking coal, quartz and their mixture, respectively, over a broad range of particle size. Results showed that using ultrasound with a relatively high energy input, acoustic cavitation occurred in water and on the surface of coal particles, and different behaviours of coal particles and quartz particles under this condition were observed: coal particles formed larger aggregates and most of them were trapped in the slurry or floated to the surface of the slurry, while quartz particles had very slight aggregation and settled down. This difference enabled good separation of coal particles from quartz particles, with high combustible recoveries and product grade over a broad particle size range tested (including 250–500 µm for coal particles). When the energy input of ultrasound was relatively low, however, no cavitation bubbles were visible, with slight aggregation and trapping of coal and quartz being observed and explained by the acoustic radiation force.

Longitudinal assessment of liver stiffness using ARFI technique does not support increased risk of fibrosis in rheumatoid arthritis patients on methotrexate.

To assess the liver stiffness in patients with rheumatoid arthritis treated with methotrexate monotherapy using non-invasive, ultrasound-based elastography (acoustic radiation force impulse (ARFI) imaging) in a longitudinal approach. In total, 23 MTX-naive patients were longitudinally assessed using acoustic radiation force impulse (ARFI) imaging. Baseline assessments were carried out between July 2018 and April 2019, and the follow-up evaluations took place after an average of 2.6years. The main outcome variable was the mean shear wave velocity as measured by the ARFI method. It was calculated from 10 valid ARFI measurements for each patient. Inferential statistical analyses (within-group comparisons) were performed using t-tests for dependent samples or suitable nonparametric procedures. The main finding was that observed ARFI shear wave velocities did not increase during the observation period. In fact, this parameter decreased over time from 1.07m/s (SD = 0.23) at baseline without MTX exposure to 0.97m/s (SD = 0.16) at follow-up after a mean of 2.6years (P = 0.013). Moreover, the magnitude of the change in shear wave velocity could not be predicted by indicators of inflammation or disease activity, BMI, age, sex or NSAR intake (corresponding regression analysis: corrected R2 = 0.344; P = 0.296). No increased risk of liver fibrosis was found in RA patients treated with MTX monotherapy during observation period.

Acoustic Radiation Force on an Eccentric Layered Fluid Sphere Exerted by a Focused Gaussian Beam

Acoustic Radiation Force on an Eccentric Layered Fluid Sphere Exerted by a Focused Gaussian Beam

Induced effects of a rigid boundary on a pulsating spherical source

This work develops a comprehensive analytical formalism to study the boundary-induced effects on a pulsating spherical radiating source near a rigid planar boundary in an inviscid fluid. Using the modal multipole expansion method, the image method and the translational addition theorem for spherical wave functions, exact closed-form expressions are derived for the dimensionless axial acoustic radiation force function as well as the radiation, amplification and extinction energy efficiency factors. The source-boundary distance and the dimensionless size parameter are especially addressed in the numerical simulations for spherical sources with different vibration modes. It is shown that the axial radiation force is positive or negative, depending on the choice of parameters. Moreover, cases when the extinction acoustic power completely vanishes are predicted theoretically for dipole and quadrupole vibrations, which can be used to achieve acoustic invisibility in acoustic cloaking devices and acoustic stealth technologies. Combination of more than one vibration modes is also investigated to better simulate the acoustic manipulation in practical applications. This work can help us understand the underlying mechanism in manipulating the active spherical radiating sources in a bounded field.

Quantitative assessment of corneal elasticity distribution after FS-LASIK using optical coherence elastography.

Quantifying corneal elasticity after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) procedure plays an important role in improving surgical safety and quality, since some latent complications may occur ascribing to changes in postoperative corneal biomechanics. Nevertheless, it is suggested that current research has been severely constrained due to the lack of an accurate quantification method to obtain postoperative corneal elasticity distribution. In this paper, an acoustic radiation force optical coherence elastography system combined with the improved phase velocity algorithm was utilized to realize elasticity distribution images of the in vivo rabbit cornea after FS-LASIK under various intraocular pressure levels. As a result, elasticity variations within and between the regions of interest could be identified precisely. This is the first time that elasticity imaging of in vivo cornea after FS-LASIK surgery was demonstrated, and the results suggested that this technology may hold promise in further exploring corneal biomechanical properties after refractive surgery.

Photoacoustic elastography based on laser-excited shear wave

Elastography can be used as a diagnostic method for quantitative characterization of tissue hardness information and thus, differential changes in pathophysiological states of tissues. In this study, we propose a new method for shear wave elastography (SWE) based on laser-excited shear wave, called photoacoustic shear wave elastography (PASWE), which combines photoacoustic (PA) technology with ultrafast ultrasound imaging. By using a focused laser to excite shear waves and ultrafast ultrasonic imaging for detection, high-frequency excitation of shear waves and noncontact elastic imaging can be realized. The laser can stimulate the tissue with the light absorption characteristic to produce the thermal expansion, thus producing the shear wave. The frequency of shear wave induced by laser is higher and the frequency band is wider. By tracking the propagation of shear wave, Young’s modulus of tissue is reconstructed in the whole shear wave propagation region to further evaluate the elastic information of tissue. The feasibility of the method is verified by experiments. Compared with the experimental results of supersonic shear imaging (SSI), it is proved that the method can be used for quantitative elastic imaging of the phantoms. In addition, compared with the SSI method, this method can realize the noncontact excitation of the shear wave, and the frequency of the shear wave excited by the laser is higher than that of the acoustic radiation force (ARF), so the spatial resolution is higher. Compared to the traditional PA elastic imaging method, this method can obtain a larger imaging depth under the premise of ensuring the imaging resolution, and it has potential application value in the clinical diagnosis of diseases requiring noncontact quantitative elasticity.

Acoustofluidic separation of prolate and spherical micro-objects

Most microfluidic separation techniques rely largely on object size as a separation marker. The ability to separate micro-objects based on their shape is crucial in various biomedical and chemical assays. Here, we develop an on-demand, label-free acoustofluidic method to separate prolate ellipsoids from spherical microparticles based on traveling surface acoustic wave-induced acoustic radiation force and torque. The freely rotating non-spherical micro-objects were aligned under the progressive acoustic field by the counterrotating radiation torque, and the major axis of the prolate ellipsoids was parallel to the progressive wave propagation. The specific alignment of the ellipsoidal particles resulted in a reduction in the cross-sectional area perpendicular to the wave propagation. As a consequence, the acoustic backscattering decreased, resulting in a decreased magnitude of the radiation force. Through the variation in radiation force, which depended on the micro-object morphology enabled the acoustofluidic shape-based separation. We conducted numerical simulations for the wave scattering of spherical and prolate objects to elucidate the working mechanism underlying the proposed method. A series of experiments with polystyrene microspheres, prolate ellipsoids, and peanut-shaped microparticles were performed for validation. Through quantitative analysis of the separation efficiency, we confirmed the high purity and high recovery rate of the proposed acoustofluidic shape-based separation of micro-objects. As a bioparticle, we utilize Thalassiosira eccentrica to perform shape-based separation, as the species has a variety of potential applications in drug delivery, biosensing, nanofabrication, bioencapsulation and immunoisolation.

Therapeutic effects of extracorporeal shock wave therapy on patients with spastic cerebral palsy and Rett syndrome: clinical and ultrasonographic findings

BackgroundExtracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases.Material and MethodsPatients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography.ResultsFifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT.ConclusionOur study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult.Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx.