Ultrasound Signals Research Articles

The Approach to Sensing the True Fetal Heart Rate for CTG Monitoring: An Evaluation of Effectiveness of Deep Learning with Doppler Ultrasound Signals.

Cardiotocography (CTG) is widely used to assess fetal well-being. CTG is typically obtained using ultrasound and autocorrelation methods, which extract periodicity from the signal to calculate the heart rate. However, during labor, maternal vessel pulsations can be measured, resulting in the output of the maternal heart rate (MHR). Since the autocorrelation output is displayed as fetal heart rate (FHR), there is a risk that obstetricians may mistakenly evaluate the fetal condition based on MHR, potentially overlooking the necessity for medical intervention. This study proposes a method that utilizes Doppler ultrasound (DUS) signals and artificial intelligence (AI) to determine whether the heart rate obtained by autocorrelation is of fetal origin. We developed a system to simultaneously record DUS signals and CTG and obtained data from 425 cases. The midwife annotated the DUS signals by auditory differentiation, providing data for AI, which included 30,160 data points from the fetal heart and 2160 data points from the maternal vessel. Comparing the classification accuracy of the AI model and a simple mathematical method, the AI model achieved the best performance, with an area under the curve (AUC) of 0.98. Integrating this system into fetal monitoring could provide a new indicator for evaluating CTG quality.

Comparison of methods for estimating Young’s moduli of mortar specimens

Precisely estimating material parameters for cement-based materials is crucial for assessing the structural integrity of buildings. Both destructive (e.g., compression test) and non-destructive methods (e.g., ultrasound, computed tomography) are used to estimate Young’s modulus. Since ultrasound estimates the dynamic Young’s modulus, a formula is required to adapt it to the static modulus. For this formulas from the literature are compared. The investigated specimens are cylindrical mortar specimens with four different sand-to-cement mass fractions of 20%, 35%, 50%, and 65%. The ultrasound signals are analyzed in two distinct ways: manual onset picking and full-waveform inversion. Full-waveform inversion involves comparing the measured signal with a simulated one and iteratively adjusting the ultrasound velocities in a numerical model until the measured signal closely matches the simulated one. Using computed tomography measurements, Young’s moduli are semi-analytically determined based on sand distribution in cement images. The reconstructed volume is segmented into sand, cement, and pores. Young’s moduli, as determined by compression tests, were better represented by full-waveform inversions (best RMSE = 0.34 GPa) than by manual onset picking (best RMSE = 0.87 GPa). Moreover, material parameters from full-waveform inversion showed less deviation than those manually picked. The maximal standard deviation of a Young’s modulus determined with FWI was 0.36, while that determined with manual picking was 1.11. Young’s moduli from computed tomography scans match those from compression tests the closest, with an RMSE of 0.13 GPa.

A numerical investigation of longitudinal wave for thermo-acoustoelastic effects on fluid-embedded in two viscoelastic layer plates at higher temperatures

Ultrasound has become indispensable for inspecting complex structures due to its efficient propagation in both liquids and solid materials. Extensive research has been conducted across various domains, encompassing wave behavior, structural interactions, material dispersion due to heterogeneity, propagation characteristics near boundaries, defect detection, and signal processing. In this context, longitudinal waves are particularly favored for examining thick components exhibiting surface defects or thermal gradients across their depth. In our current work, we employed a numerical approach based on the Transfer Matrix Method (TMM) to model ultrasound signals backscattered under normal incidence by a multilayer structure immersed in water. This method involves representing each layer using a quadrupole formalism that combines stresses and velocities. Simultaneously, we harnessed the thermodynamic equation for aqueous solutions and Fourier’s law to derive the expression for the thermo-acoustic coefficient of longitudinal waves within a fluid embedded between two parallel immersed plates, enabling precise control of the fluid temperature over a range from 0 °C to 700 °C. In the time domain, we evaluated the ultrasonic parameters of a fluid exposed to a temperature range from 0 to 700 °C. This evaluation was supported by a variety of multilayer structures designed to ensure the accurate processing of backscattered signals. These structures were excited by longitudinal waves, with a central frequency fixed at 5 MHz. The results obtained emphasize the sensitivity of longitudinal waves to temperature variations and reveal the presence of wave dispersion induced by temperature fluctuations. In order to investigate this dispersion, we conducted an extensive study of ultrasonic longitudinal wave propagation across a range of excitation frequencies from 2 to 12 MHz. This study encompassed the calculation of phase and group velocities, as well as the corresponding attenuation. The results confirm the relevance of our research to various applications and highlight the complex interaction between longitudinal wave dispersion and temperature variations.

Investigating the potential of catheter-assisted pulsed focused ultrasound ablation for atherosclerotic plaques.

Atherosclerosis is a condition in which an adhesive substance called plaque accumulates over time inside the arteries. Plaque buildup results in the constriction of arteries, causing a shortage of blood supply to tissues and organs. Removing atherosclerotic plaques controls the development of acute ischemic stroke and heart diseases. It remains imperative for positive patient outcomes. This study sought to develop a minimally invasive technique for removing arterial plaques by applying focused ultrasound (FUS) energy on the metal surface of a nitinol catheter wire to induce inertial cavitation. The induced cavitation can deplete plaque mechanically inside the arteries, leading towards improved recanalization of blood vessels. The enhanced cavitation effect induced by combining FUS with a metal catheter was first verified by exposing agar phantom gels with or without a 0.9-mm diameter nitinol wire to an acoustic field produced by a 0.5-MHz FUS transducer. The phenomenon was further confirmed in pork belly fat samples with or without a 3-mm diameter nitinol catheter wire. Cavitation was monitored by detecting the peaks of emitted ultrasound signals from the samples using a passive cavitation detector (PCD). Cavitation threshold values were determined by observing the jump in the peak amplitude of signals received by the PCD when the applied FUS peak negative pressure (PNP) increased. To simulate arterial plaque removal, FUS with or without a catheter was used to remove tissues from pork belly fat samples and the lipid cores of human atherosclerotic plaque samples using 2500-cycle FUS bursts at 10% duty cycle and a burst repetition rate of 20Hz. Treatment outcomes were quantified by subtracting the weight of samples before treatment from the weight of samples after treatment. All measurements were repeated 5 times (n=5) unless otherwise indicated, and paired t-tests were used to compare the means of two groups. A p-value of <0.05 will be considered significant. Our results showed that with a nitinol wire, the cavitation threshold in agar phantoms was reduced to 2.6MPa from 4.3MPa PNP when there was no nitinol wire in the focal region of FUS. For pork belly fat samples, cavitation threshold values were 1.0 and 2.0MPa PNP, with and without a catheter wire, respectively. Pork belly fat tissues and lipid cores of atherosclerotic plaques were depleted at the interface between a catheter and the samples at 2 and 4MPa FUS PNP, respectively. The results showed that with a catheter wire in the focal region of a 3-min FUS treatment session, 24.7 and 25.6mg of lipid tissues were removed from pork belly fat and human atherosclerotic samples, respectively. In contrast, the FUS-only group showed no reduction in sample weight. The differences between FUS-only and FUS-plus-catheter groups were statistically significant (p<0.001 for the treatment on pork belly samples, and p<0.01 for the treatment on human atherosclerotic samples). This study demonstrated the feasibility of catheter-assisted FUS therapy for removing atherosclerotic plaques.

Reduced Training Data for Laser Ultrasound Signal Interpretation by Neural Networks

The performance of machine learning algorithms is conditioned by the availability of training datasets, which is especially true for the field of nondestructive evaluation. Here we propose one reconfigurable specimen instead of numerous reference specimens with known, unchangeable defect properties, which are usually complicated to fabricate. It consist of a shape memory polymer foil with temperature-dependent Young’s modulus and ultrasound attenuation. This open a possibility to generate a reconfigurable defect by projecting a heating laser in the form of a short line on the specimen surface. Ultrasound is generated by a laser pulse at one fixed position and detected by a laser vibrometer at another fixed position for 64 different defect positions and 3 different configurations of the specimen. The obtained diversified datasets are used to optimize the neural network architecture for the interpretation of ultrasound signals. We study the performance of the model in cases of reduced and dissimilar training datasets. In our first study, we classify the specimen configurations with the defect position being the disturbing parameter. The model shows high performance on a dataset of signals obtained at all the defect positions, even if trained on a completely different dataset containing signals obtained at only few defect positions. In our second study, we perform precise defect localization. The model becomes robust to the changes in the specimen configuration when a reduced dataset, containing signals obtained at two different specimen configurations, is used for the training process. This work highlights the potential of the demonstrated machine learning algorithm for industrial quality control. High-volume products (simulated by a reconfigurable specimen in our work) can be rapidly tested on the production line using this single-point and contact-free laser ultrasonic method.

Complexin-1 enhances ultrasound neurotransmission in the mammalian auditory pathway.

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.

A mesoporous theranostic platform for ultrasound and photoacoustic dual imaging-guided photothermal and enhanced starvation therapy for cancer

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O2) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. Statement of significanceA multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor.

Sensing to Hear through Memory

Speech enhancement on mobile devices is a very challenging task due to the complex environmental noises. Recent works using lip-induced ultrasound signals for speech enhancement open up new possibilities to solve such a problem. However, these multi-modal methods cannot be used in many scenarios where ultrasound-based lip sensing is unreliable or completely absent. In this paper, we propose a novel paradigm that can exploit the prior learned ultrasound knowledge for multi-modal speech enhancement only with the audio input and an additional pre-enrollment speaker embedding. We design a memory network to store the ultrasound memory and learn the interrelationship between the audio and ultrasound modality. During inference, the memory network is able to recall the ultrasound representations from audio input to achieve multi-modal speech enhancement without needing real ultrasound signals. Moreover, we introduce a speaker embedding module to further boost the enhancement performance as well as avoid the degradation of the recalling when the noise level is high. We adopt an end-to-end multi-task manner to train the proposed framework and perform extensive evaluations on the collected dataset. The results show that our method yields comparable performance with audio-ultrasound methods and significantly outperforms the audio-only methods.

Multimodal PA/US imaging in Rheumatoid Arthritis: Enhanced correlation with clinical scores

BackgroundAccurate assessment of Rheumatoid Arthritis (RA) activity remains a challenge. Multimodal photoacoustic/ultrasound (PA/US) joint imaging emerges as a novel imaging modality capable of depicting microvascularization and oxygenation levels in inflamed joints associated with RA. However, the scarcity of large-scale studies limits the exploration of correlating joint oxygenation status with disease activity. ObjectiveThis study aimed to explore the correlation between multimodal PA/US imaging scores and RA disease activity, assessing its clinical applicability in managing RA. MethodsIn this study, we recruited 111 patients diagnosed with RA and conducted examinations of seven small joints on their clinically dominant side using a PA/US imaging system. The PA and power Doppler ultrasound (PDUS) signals were semi-quantitatively assessed using a 0–3 grading system. The cumulative scores for PA and PDUS across these seven joints (PA-sum and PDUS-sum) were calculated. Relative oxygen saturation (So2) values of inflamed joints on the clinically dominant side were measured, and categorized into four distinct PA+So2 patterns. The correlation between PA/US imaging scores and disease activity indices was systematically evaluated. ResultsAnalysis of 777 small joints in 111 patients revealed that the PA-sum scores exhibited a strong positive correlation with standard clinical scores for RA, including DAS28 [ESR] (ρ = 0.682), DAS28 [CRP] (ρ = 0.683), CDAI (ρ = 0.738), and SDAI (ρ = 0.739), all with p < 0.001. These correlations were superior to those of the PDUS-sum scores (DAS28 [ESR] ρ = 0.559, DAS28 [CRP] ρ = 0.555, CDAI ρ = 0.575, SDAI ρ = 0.581, p < 0.001). Significantly, in patients with higher PA-sum scores, notable differences were observed in the erythrocyte sedimentation rate (ESR) (p < 0.01) and swollen joint count 28 (SJC28) (p < 0.01) between hypoxia and intermediate groups. Notably, RA patients in the hypoxia group exhibited higher clinical scores in certain clinical indices. ConclusionMulti-modal PA/US imaging introduces potential advancements in RA assessment, especially regarding So2 evaluations in synovial tissues and associated PA scores. However, further studies are warranted, particularly with more substantial sample sizes and in multi-center settings. SummaryThis study utilized multi-modal PA/US imaging to analyze Rheumatoid Arthritis (RA) patients' synovial tissues and affected joints. When juxtaposed with traditional PDUS imaging, the PA approach demonstrated enhanced sensitivity, especially concerning detecting small vessels in thickened synovium and inflamed tendon sheaths. Furthermore, correlations between the derived PA scores, PA+So2 patterns, and standard clinical RA scores were observed. These findings suggest that multi-modal PA/US imaging could be a valuable tool in the comprehensive assessment of RA, offering insights not only into disease activity but also into the oxygenation status of synovial tissues. However, as promising as these results are, further investigations, especially in larger and diverse patient populations, are imperative. Key points⸸ Multi-modal PA/US Imaging in RA: This novel technique was used to assess the So2 values in synovial tissues and determine PA scores of affected RA joints.⸸ Correlation significantly with Clinical RA Scores: Correlations significantly were noted between PA scores, PA+So2 patterns, and standard clinical RA metrics, hinting at the potential clinical applicability of the technique.

Evaluation of inversion approaches for plates based on guided waves and modal analysis

The identification of defects in plate-like structures has been successfully treated using both local guided ultrasonic waves and global modal quantities. Although there are many papers on these techniques, a lack of comparability between the two methods persists. This makes it difficult for users to identify the most appropriate method for the defect in question. This paper examines the effect of different parameterizations of a circular defect in a square aluminum plate on the system response in a case study. The measured local ultrasound signal from a propagating guided wave makes up the initial data set. The first method uses the entire waveform for the objective function of the optimization problem, while the second considers the velocity of the A0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$A_0$$\\end{document} mode. In the third and fourth methods, the first and second global natural frequencies of the plate modeled with free-free boundary conditions are investigated. The numerical models are validated experimentally through measurements with a laser Doppler vibrometer. This results in the qualitative and quantitative evaluation of the objective functions for all parameter combinations of the defect. The recommendation to sequentially employ modal analysis and then the ultrasound procedure is made for the defect type used in this study. The data gathered on the objective functions suggests that potential joint employment of the natural frequency and ultrasound methods may increase computational efficiency. For a specific case, the methods could also complement each other in terms of challenges such as local minima.

Appropriate indicator of modeling error for threshold-based model selection in statistics-based ultrasound tissue characterization

Analysis of the envelope statistics of ultrasound echo signals contributes to quantitative tissue characterization in medical ultrasound. Many probability distribution model functions have been studied, and the model function that should be used for tissue characterization depends on the type of disease, even in the same organ. Thus, an appropriate model selection is important for an accurate diagnosis. In this study, we aimed to select a model using threshold processing for modeling errors instead of a simple selection by minimizing the modeling error. For this purpose, we compared several indicators of modeling errors using random number simulations, ultrasonic simulation, and phantom experiment. The results validated that the Mahalanobis distance of moments is an appropriate indicator because it enables the use of a constant threshold value, regardless of the type of model function and data length.

Effect of low-intensity focused ultrasound therapy on postpartum uterine involution in puerperal women: A randomized controlled trial.

Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

Reconstruction of elasticity modulus distribution base on semi-supervised neural network

Accurate reconstruction of tissue elasticity modulus distribution has always been an important challenge in ultrasound elastography. Considering that existing deep learning-based supervised reconstruction methods only use simulated displacement data with random noise in training, which cannot fully provide the complexity and diversity brought by in-vivo ultrasound data, this study introduces the use of displacement data obtained by tracking in-vivo ultrasound radio frequency signals (i.e., real displacement data) during training, employing a semi-supervised approach to enhance the prediction accuracy of the model. Experimental results indicate that in phantom experiments, the semi-supervised model augmented with real displacement data provides more accurate predictions, with mean absolute errors and mean relative errors both around 3%, while the corresponding data for the fully supervised model are around 5%. When processing real displacement data, the area of prediction error of semi-supervised model was less than that of fully supervised model. The findings of this study confirm the effectiveness and practicality of the proposed approach, providing new insights for the application of deep learning methods in the reconstruction of elastic distribution from in-vivo ultrasound data.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment.

Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment.In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

On the feasibility of ultrasonic full waveform evaluation with changing testing conditions for the quality control of manufacturing parts

ABSTRACT Fast volumetric non-destructive testing methods are needed, especially for quality control in manufacturing lines. Ultrasonic testing with full waveform evaluation is a promising method for this. However, changes in coupling conditions or environmental factors can significantly alter the ultrasound signal, sometimes more than actual defects. This study investigates the effect of various factors on the ultrasound signal based on a Monte Carlo study with wavefield simulations. The test specimens comprise aluminium plates with holes of varying sizes and positions. Using both experimental as well as simulated data, the performance of two commonly used comparison metrics, namely the R 2 score and the magnitude-squared coherence integral, for detecting defects in manufactured parts is evaluated. It was found that the magnitude-squared coherence integral is more robust against random influences than the R 2 score. Additionally, factors influencing the entire plate exhibit the most significant impact on the signals. The hole positions and dimensions change the signals and the value of the comparison metrics significantly and are difficult to distinguish by one metric. A deep learning model, however, is capable of performing this task and it outperforms the comparison metrics in defect detection. The performance of the approaches is assessed with probability of detection curves.

Noninvasive Bolus Transit Detection in Cervical Esophagus Utilizing Ultrasound Characteristics.

This pilot study aims to identify characteristic A-mode ultrasound features relevant to noninvasive detection of esophageal bolus transit in the proximal esophagus. Ultrasound signals at a lateral neck site were obtained via a single-element ultrasonic transducer with synchronous videofluoroscopic swallowing studies images of swallows of differing viscosities in 21 adult dysphagia outpatients. Characteristic ultrasound features were extracted to differentiate a bolus-filled from a collapsed esophagus. From 21 subjects, 412 swallows exhibited 4 reproducible waveform patterns associated with bolus transit as displayed in a heatmap: (1)Strong Reflectors; (2)Echo Shifts; (3)Distal Acoustic Enhancement; and (4)Speckling: One or more of these features were observed in the swallow series for all 21 subjects. Distinct acoustic waveform features acquired by single-element ultrasonic transducers can identify bolus transit through the cervical esophagus.

181 Initial Experience With Sonodynamic Therapy Using Low-Intensity Focused Ultrasound and ALA for Pediatric Patients With Diffuse Intrinsic Pontine Glioma

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor with poor prognosis. Aminolevulinic acid (ALA) sonodynamic therapy (SDT) is a non-invasive strategy where tissues sensitized with ALA are exposed to MR-guided focused ultrasound (MRgFUS). Preclinical studies have demonstrated significant slowing in growth of gliomas and increased survival in animal models. METHODS: A Phase1/2 study (NCT05123534, clinicaltrials.gov) in patients with newly diagnosed DIPG is ongoing. MRIs at 24hrs and 1- and 3-months post procedure are obtained to evaluate safety and efficacy. A total of 18-45 patients will be enrolled in 9 different dose-escalation cohorts. The three patients from the first cohort are described below. RESULTS: Three patients with DIPGs were treated with 5 mg/kg of ALA and 200 J of MRgFUS in the first cohort. They were aged 5-7 years and 2 were females. They had received radiotherapy 8-10 weeks prior and interval imaging showed no disease progression. The first patient received two treatments with one half of the pons treated during each visit. The other two received one treatment targeting the entire pons. They all tolerated the procedure well. One of the patients noted a transient worsening of his diplopia after the treatment. No significant edema or hemorrhage were noted on postoperative scans obtained within 24 hrs of treatment. MRIs obtained 1- and 3-months after treatment have shown significant decrease in tumor burden in 2 of the patients. CONCLUSIONS: The first-in-human experience with a new therapeutic modality for DIPG patients demonstrates safety and efficacy. Future procedures will involve ascending drug and MRgFUS energy dose combinations. The use of focused ultrasound signals an innovative approach for challenging to treat pediatric brain tumors.

Computing Speed-of-Sound From Ultrasound: User-Agnostic Recovery and a New Benchmark.

Medical ultrasound is one of the most accessible imaging modalities, but is a challenging modality for quantitative parameters comparison across vendors and sonographers. B-Mode imaging, with limited exceptions, provides a map of tissue boundaries; crucially, it does not provide diagnostically relevant physical quantities of the interior of organ domains.This can be remedied: the raw ultrasound signal carries significantly more information than is present in the B-Mode image. Specifically, the ability to recover speed-of-sound and attenuation maps from the raw ultrasound signal transforms the modality into a tissue-property modality. Deep learning was shown to be a viable tool for recovering speed-of-sound maps. A major hold-back towards deployment is the domain transfer problem, i.e., generalizing from simulations to real data. This is due in part to dependence on the (hard-to-calibrate) system response. We explore a remedy to the problem of operator-dependent effects on the system response by introducing a novel approach utilizing the phase information of the IQ demodulated signal. We show that the IQ-phase information effectively decouples the operator-dependent system response from the data, significantly improving the stability of speed-of-sound recovery. We also introduce an improvement to the network topology providing faster and improved results to the state-of-the-art. We present the first publicly available benchmark for this problem: a simulated dataset for raw ultrasound plane wave processing. The consideration of the phase of the IQ-signals presents a promising appeal to traversing the transfer learning problem, advancing the goal of real-time speed-of-sound imaging.

In vivo bistatic dual-aperture ultrasound imaging and elastography of the abdominal aorta.

Introduction: In this paper we introduce in vivo multi-aperture ultrasound imaging and elastography of the abdominal aorta. Monitoring of the geometry and growth of abdominal aortic aneurysms (AAA) is paramount for risk stratification and intervention planning. However, such an assessment is limited by the lateral lumen-wall contrast and resolution of conventional ultrasound. Here, an in vivo dual-aperture bistatic imaging approach is shown to improve abdominal ultrasound and strain imaging quality significantly. By scanning the aorta from different directions, a larger part of the vessel circumference can be visualized. Methods: In this first-in-man volunteer study, the performance of multi-aperture ultrasound imaging and elastography of the abdominal aortic wall was assessed in 20 healthy volunteers. Dual-probe acquisition was performed in which two curved array transducers were aligned in the same imaging plane. The transducers alternately transmit and both probes receive simultaneously on each transmit event, which allows for the reconstruction of four ultrasound signals. Automatic probe localization was achieved by optimizing the coherence of the trans-probe data, using a gradient descent algorithm. Speckle-tracking was performed on the four individual bistatic signals, after which the respective axial displacements were compounded and strains were calculated. Results: Using bistatic multi-aperture ultrasound imaging, the image quality of the ultrasound images, i.e., the angular coverage of the wall, was improved which enables accurate estimation of local motion dynamics and strain in the abdominal aortic wall. The motion tracking error was reduced from 1.3 mm ± 0.63 mm to 0.16 mm ± 0.076 mm, which increased the circumferential elastographic signal-to-noise ratio (SNRe) by 12.3 dB ± 8.3 dB on average, revealing more accurate and homogeneous strain estimates compared to single-perspective ultrasound. Conclusion: Multi-aperture ultrasound imaging and elastography is feasible in vivo and can provide the clinician with vital information about the anatomical and mechanical state of AAAs in the future.

Genetic Modulation of Biosynthetic Gas Vesicles for Ultrasound Imaging.

Gas vesicles (GVs) from microorganisms are genetically air-filled protein nanostructures, and serve as a new class of nanoscale contrast agents for ultrasound imaging. Recently, the genetically encoded GV gene clusters have been heterologously expressed in Escherichia coli, allowing these genetically engineered bacteria to be visualized in vivo in a real-time manner by ultrasound. However, most of the GV genes remained functionally uncharacterized, which makes it difficult to regulate and modify GVs for broad medical applications. Here, the impact of GV proteins on GV formation is systematically investigated. The results first uncovered that the deletions of GvpR or GvpU resulted in the formation of a larger proportion of small, biconical GVs compared to the full-length construct, and the deletion of GvpT resulted in a larger portion of large GVs. Meanwhile, the combination of gene deletions has resulted in several genotypes of ultrasmall GVs that span from 50 to 20nm. Furthermore, the results showed that E. coli carrying the ΔGvpCRTUmutant can produce strong ultrasound contrast signals in mouse liver. In conclusion, the study provides new insights into the roles of GV proteins in GV formation and produce ultrasmall GVs with a wide range of in vivo research.