GHz ultrasonic sensor for ionic content with high sensitivity and localization.

Sensing the ionic content of a solution at high spatial and temporal resolution and sensitivity is a challenge in nanosensing. This paper describes a comprehensive investigation of the possibility of GHz ultrasound acoustic impedance sensors to sense the content of an ionic aqueous medium. At the 1.55 GHz ultrasonic frequency used in this study, the micron-scale wavelength and the decay lengths in liquid result in a highly localized sense volume with the added potential for high temporal resolution and sensitivity. The amplitude of the back reflected pulse is related to the acoustic impedance of the medium and a function of ionic species concentration of the KCl, NaCl, and CaCl2 solutions used in this study. A concentration sensitivity as high as 1 mM and concentration detection range of 0 to 3 M was achieved. These bulk acoustic wave pulse-echo acoustic impedance sensors can also be used to record dynamic ionic flux.

Comprehensive integrated analysis of MR and DCE-MR radiomics models for prognostic prediction in nasopharyngeal carcinoma.

Although prognostic prediction of nasopharyngeal carcinoma (NPC) remains a pivotal research area, the role of dynamic contrast-enhanced magnetic resonance (DCE-MR) has been less explored. This study aimed to investigate the role of DCR-MR in predicting progression-free survival (PFS) in patients with NPC using magnetic resonance (MR)- and DCE-MR-based radiomic models. A total of 434 patients with two MR scanning sequences were included. The MR- and DCE-MR-based radiomics models were developed based on 289 patients with only MR scanning sequences and 145 patients with four additional pharmacokinetic parameters (volume fraction of extravascular extracellular space (ve), volume fraction of plasma space (vp), volume transfer constant (Ktrans), and reverse reflux rate constant (kep) of DCE-MR. A combined model integrating MR and DCE-MR was constructed. Utilizing methods such as correlation analysis, least absolute shrinkage and selection operator regression, and multivariate Cox proportional hazards regression, we built the radiomics models. Finally, we calculated the net reclassification index and C-index to evaluate and compare the prognostic performance of the radiomics models. Kaplan-Meier survival curve analysis was performed to investigate the model's ability to stratify risk in patients with NPC. The integration of MR and DCE-MR radiomic features significantly enhanced prognostic prediction performance compared to MR- and DCE-MR-based models, evidenced by a test set C-index of 0.808 vs 0.729 and 0.731, respectively. The combined radiomics model improved net reclassification by 22.9%-52.6% and could significantly stratify the risk levels of patients with NPC (p = 0.036). Furthermore, the MR-based radiomic feature maps achieved similar results to the DCE-MR pharmacokinetic parameters in terms of reflecting the underlying angiogenesis information in NPC. Compared to conventional MR-based radiomics models, the combined radiomics model integrating MR and DCE-MR showed promising results in delivering more accurate prognostic predictions and provided more clinical benefits in quantifying and monitoring phenotypic changes associated with NPC prognosis.

GHz Ultrasound and Electrode Chip-Scale Arrays Stimulate and Influence Morphology of Human Neural Cells.

This study describes the effects of chip-scale gigahertz (GHz) ultrasound (US) and electrical stimulus on the morphology, functionality, and viability of neural cells in vitro. The GHz frequency stimulation is achieved using aluminum nitride piezoelectric transducers fabricated on a silicon wafer, operating at 1.47 GHz, corresponding to the film's thickness mode resonance. These devices are used to stimulate SH-SY5Y neural cells in vitro and observe effects on the morphology and viability of the stimulated cells. It is possible to use these devices to deliver either ultrasonic stimulus alone or US stimulus in conjunction with electrical stimulus. Viability tests demonstrated that the neurons retained structural integrity and viability across a wide range of GHz US stimulus intensities (0-1.2 W/cm2), validating that measurements occur at nontoxic doses of US. Neural stimulation is validated with these devices following the outputs of a previous study, with the normalized fluorescence intensity of activated cells between 1.9 and 2.4. The 300-s ultrasonic stimulation at 1.47 GHz and 0.05 W/cm2 peak intensity led to a decrease in nuclear elongation by 17.5% and a cross-sectional area decrease by 17.8% across three independent trials of over 150 cells per category ( ). The F-actin governed cellular elongation increased in length by up to 16.3% in cells exposed to an ultrasonic stimulus or costimulus ( ). Neurite length increased following ultrasonic stimulation compared with control by 75.8% ( ). This article demonstrates new GHz US and electrical chip-scale arrays with apparent effects in both neural excitation and cell morphology.

Mapping white matter structural and network alterations in betel quid-dependent chewers using high angular resolution diffusion imaging.

Background: To evaluate brain white matter diffusion characteristics and anatomical network alterations in betel quid dependence (BQD) chewers using high angular resolution diffusion imaging (HARDI). Methods: The current study recruited 53 BQD chewers and 37 healthy controls (HC) in two groups. We explored regional diffusion metrics alternations in the BQD group compared with the HC group using automated fiber quantification (AFQ). We further employed the white matter (WM) anatomical network of HARDI to explore connectivity alterations in BQD chewers using graph theory. Results: BQD chewers presented significantly lower FA values in the left and right cingulum cingulate, the left and right thalamic radiation, and the right uncinate. The BQD has a significantly higher RD value in the right uncinate fasciculus than the HC group. At the global WM anatomical network level, global network efficiency (p = 0.008) was poorer and Lp (p = 0.016) was greater in the BQD group. At the nodal WM anatomical network level, nodal efficiency (p < 0.05) was lower in the BQD group. Conclusion: Our findings provide novel morphometric evidence that brain structural changes in BQD are characterized by white matter diffusivity and anatomical network connectivity among regions of the brain, potentially leading to the enhanced reward system and impaired inhibitory control.

Dynamic contrast-enhanced MRI predicts PTEN protein expression which can function as a prognostic measure of progression-free survival in NPC patients.

OBJECTIVES: The objective of our study was to investigate whether a phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression was associated with dynamic contrast-enhanced MRI (DCE-MRI) parameters and prognosis in nasopharyngeal carcinoma (NPC). METHODS: Two-hundred-and-forty-five (245) patients with NPC who underwent pretreatment biopsy, expression of PTEN detected by immunohistochemistry of biopsy, and radical intensity-modulated radiation therapy (IMRT) with or without chemotherapy were included. Tumor segmentations were delineated on pretreatment MRI manually. The pharmacokinetic parameters (Ktrans, Kep, Ve, and Vp) derived from dynamic contrast-enhanced MRI (DCE-MRI) using the extended Toft's model within the tumor segmentations were estimated. The following demographics and clinical features were assessed and correlated against each other: gender, age, TNM stage, clinical-stage, Epstein-Barr virus (EBV), pathological type, progression-free survival (PFS), and prognosis status. DCE parameter evaluation and clinical feature comparison between the PTEN positive and negative groups were performed and correlation between PTEN expression with the PFS and prognosis status using Cox regression for survival analysis were assessed. RESULTS: A significantly lower Ktrans and Kep were found in NPC tumors in PTEN negative patients than in PTEN positive patients. Ktrans performed better than Kep in detecting PTEN expression with the ROC AUC of 0.752. PTEN negative was associated with later TNM stage, later clinical-stage, shorter PFS, and worse prognosis. Moreover, N stage, pathological type, Kep, and prognostic status can be considered as independent variables in discrimination of PTEN negative expression in NPCs. CONCLUSIONS: PTEN negative indicated a shorter PFS and worse prognosis than PTEN positive in NPC patients. Ktrans and Kep derived from DCE-MRI, which yielded reliable capability, may be considered as potential imaging markers that are correlated with PTEN expression and could be used to predict PTEN expression noninvasively. Combined radiological and clinical features can improve the performance of the classification of PTEN expression.

GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells.

Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10-20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves [Formula: see text] caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03 oC for [Formula: see text] This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.

Spatially Adaptive Regularization in Total Field Inversion for Quantitative Susceptibility Mapping.

Adaptive Total Field Inversion is described for quantitative susceptibility mapping (QSM) reconstruction from total field data through a spatially adaptive suppression of shadow artifacts through spatially adaptive regularization. The regularization for shadow suppression consists of penalizing low-frequency components of susceptibility in regions of small susceptibility contrasts as estimated by R2∗ derived signal intensity. Compared with a conventional local field method and two previously proposed regularized total field inversion methods, improvements were demonstrated in phantoms and subjects without and with hemorrhages. This algorithm, named TFIR, demonstrates the lowest error in numerical and gadolinium phantom datasets. In COSMOS data, TFIR performs well in matching ground truth in high-susceptibility regions. For patient data, TFIR comes close to meeting the quality of the reference local field method and outperforms other total field techniques in both clinical scores and shadow reduction.

Early Stage Markers of Late Delayed Neurocognitive Decline Using Diffusion Kurtosis Imaging of Temporal Lobe in Nasopharyngeal Carcinoma Patients.

Purpose: To determine whether the early assessment of temporal lobe microstructural changes using diffusion kurtosis imaging (DKI) can predict late delayed neurocognitive decline after radiotherapy in nasopharyngeal carcinoma (NPC) patients. Methods and Materials: Fifty-four NPC patients undergoing intensity-modulated radiotherapy (IMRT) participated in a prospective DKI magnetic resonance (MR) imaging study. MR imaging was acquired prior to IMRT (-0), 1 month (-1), and 3 (-3) months after IMRT. Kurtosis (Kmean, Kax, Krad) and Diffusivity (Dmean, Dax, Drad) variables in the temporal lobe gray and white matter were computed. Neurocognitive function tests (MoCA) were administered pre-radiotherapy and at 2 years post-IMRT follow-up. All the patients were divided into neurocognitive function decline (NFD group) and neurocognitive function non-decline groups (NFND group) according to whether the MoCA score declined ≥3 2 years after IMRT. All the DKI metrics were compared between the two groups, and the best imaging marker was chosen for predicting a late delayed neurocognitive decline. Results: Kurtosis (Kmean-1, Kmean-3, Kax-1, Kax-3, Krad-1, and Krad-3) and Diffusivity (Dmean-1 and Dmean-3) of white matter were significantly different between the two groups (p<0.05). Axial Kurtosis (Kax-1, Kax-3) of gray matter was significantly different between the two groups (p<0.05). By receiver operating characteristic (ROC) curves, Kmean-1 of white matter performed best in predicting of MoCA scores delayed decline (p<0.05). The radiation dose was also significantly different between NFD and NFND group (p=0.031). Conclusions: Temporal lobe white matter is more vulnerable to microstructural changes and injury following IMRT in NPC. Metrics derived from DKI should be considered as imaging markers for predicting a late delayed neurocognitive decline. Both temporal lobe white and gray matter show microstructural changes detectable by DKI. The Kmean early after radiotherapy has the best prediction performance.

Temporal lobe microstructural abnormalities in patients with nasopharyngeal carcinoma quantitatively evaluated by high-resolution DWI and DKI after concurrent chemoradiotherapy.

PURPOSE: To investigate temporal lobe microstructural abnormalities and neurocognitive function impairment after concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: NPC patients who underwent CCRT were enrolled. High-resolution diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) and diffusion-kurtosis imaging (DKI) MRI, were performed 5 times per patient (once pre-CCRT, 1 week post-CCRT, 3 months post-CCRT, 6 months post-CCRT, and 12 months post-CCRT). Neurocognitive function was evaluated by Montreal Neurocognitive Assessment (MoCA) twice per patient, once pre-CCRT, and once 12-months after CCRT. RESULTS: Of 111 patients, 56 completed the entire protocol. The MRI derived apparent diffusion coefficient (ADC), mean of diffusion coefficient (Dmean) and fractional anisotropy (FA) values were significantly decreased (p < 0.05) over the 0-3 month period following CCRT and significantly increased (p < 0.05) over the 3-12 month period following CCRT. The mean of kurtosis coefficient (Kmean) continued to decline over a year post-CCRT. All parameters reveal more pronounced changes in white matter (WM) than in grey matter (GM). MoCA also declined after CCRT (p < 0.001). MoCA showed significant positive correlation with Kmean-WM-6 m, Kmean-WM-12 m and ΔKmean-WM. CONCLUSIONS: High-resolution DWI and DKI should be considered as a promising method for the investigation of temporal lobe microstructural change in NPC patients after CCRT.

Micro- and Ultrastructural Characterization of Age-Related Changes at the Anterior Cruciate Ligament-to-Bone Insertion.

There remains a lack of understanding of the structural changes that occur across the complex, multitissue anterior cruciate ligament (ACL)-to-bone insertion as a function of aging. The objective of this study is to provide a multiscale comparison of matrix properties across the skeletally immature and mature ACL-to-bone insertion. Using complementary imaging methods, micro- and ultrastructural analysis of the insertion revealed that collagen fiber orientation at the interface changes with age, though the degree of collagen organization is maintained over time. These changes are accompanied by a decrease in collagen fibril density and are likely driven by physiological loading. Mineral crystal structure and crystallinity are conserved over time, despite regional differences in crystallinity between the interface and bone. This suggests that mineral chemistry is established early in development and underscores its important functional role. Collectively, these findings provide new insights into interface development and set critical design benchmarks for integrative soft tissue repair.

Nuclear elongation correlates with neurite induced cellular elongation during differentiation of SH-SY5Y neural cells / El alargamiento del núcleo se correlaciona con el alargamiento celular inducido por neuritas durante la diferenciación de las células neuronales Sh-Sy5Y

SUMMARY: Cellular differentiation is a highly regulated process that has vast implications for the mechanics of the cell. The interplay between differentiation induced cytoskeletal mechanical changes and strain on the nucleus is a potential cause of gene level changes. This study explores mechanical changes in SH-SY5Y neural cells during differentiation mediated by Retinoic Acid (RA) across Days 0 through 9. Findings suggest that cellular elongation increases 1.92-fold over a 10-day differentiation period, from 48.97 ±16.85µm to 93.96 ± 31.20 µm over 3 repeated trials and across multiple cells analyzed on ImageJ. Nuclear elongation increases less substantially from 17.51 ± 2.71 µm to 23.26 ± 3.10 µm over 3 repeated trials and across multiple cells. Results are statistically significant at a significance level of α = 0.05. This study is one of the first studies to show that during the process of RA mediated neural differentiation in SH-SY5Y neural cells, nuclear elongation is initially not significantly correlated with cellular elongation, but it becomes correlated during the differentiation process with an overall correlation coefficient of 0.4498 at a significance level of α = 0.05. Given the time course of the mechanical changes and the known coupling between the cytoskeleton and nuclear lamina, this study suggests a causative and correlative relationship between neurite-driven cellular elongation and nuclear elongation during neural differentiation.

RESUMEN: La diferenciación celular es un proceso altamente regulado que tiene vastas implicaciones para la mecánica de la célula. La interacción entre los cambios mecánicos citoesqueléticos inducidos por la diferenciación y la tensión en el núcleo es una causa potencial de cambios a nivel genético. Este estudio explora los cambios mecánicos en las células neurales SH-SY5Y durante la diferenciación mediada por el ácido retinoico (RA) durante los días 0 a 9. Los resultados sugieren que el alargamiento celular aumenta 1,92 veces durante un período de diferenciación de 10 días, de 48,97 ± 16,85 µm a 93,96 ± 31,20 µm en 3 ensayos repetidos y en múltiples células analizadas en Image J. El alargamiento nuclear aumenta menos sustancialmente de 17,51 ± 2,71 µm a 23,26 ± 3,10 µm durante 3 ensayos repetidos y en múltiples células. Los resultados son estadísticamente significativos a un nivel de significancia de α = 0,05. Esta investigación es uno de los primeros estudios en demostrar que durante el proceso de diferenciación neural mediada por RA en las células neurales SH-SY5Y, el alargamiento nuclear inicialmente no se correlaciona significativamente con el alargamiento celular, pero se correlaciona durante el proceso de diferenciación con un coeficiente de correlación global de 0,4498 a un nivel de significancia de α = 0,05. Dado el curso temporal de los cambios mecánicos y el acoplamiento conocido entre el citoesqueleto y la lámina nuclear, este estudio sugiere una relación causal y correlativa entre el alargamiento celular impulsado por neuritas y el alargamiento nuclear durante la diferenciación neural.

Characterization of SH-SY5Y neurons subject to 92kHz ultrasound stimulation / Caracterización de neuronas SH-SY5Y sujetas a estimulación por ultrasonido de 92 kHz

SUMMARY: Cellular microstructural changes due to ultrasound exposure are critical to understand and characterize in order to further the establishment of ultrasonics in cell and tissue engineering and medicine. In this study, neurite length, nuclear morphology, and cellular toxicity are assessed at varying intensities of 92 kHz ultrasound provided by a piezoceramic disk element and incident upon SH- SY5Y neurons in vitro. Findings suggest that stimulation increases neurite length up to 2.73 fold tested at α = 0.05 in an intensity dependent manner. Additionally, stimulation causes a statistically significant (α = 0.05) decrease in nuclear area and less elongated nuclei, by 1.78 fold and 1.38 fold respectively, also in an intensity dependent manner. For maximum transducer surface intensities ranging from 0 to 39.11 W/cm2, the toxicity of 92 kHz ultrasound is assessed and a nontoxic range is determined using Caspase-3 and Annexin V staining, in addition to Calcium imaging via Calcein-AM staining. Intensities of up to 1.6 W/cm2 are found to be nontoxic for the cells under the parameters used in this study.

RESUMEN: Los cambios micro estructurales celulares debidos a la exposición a los ultrasonidos son fundamentales para comprender y caracterizar el establecimiento de los ultrasonidos en la ingeniería y la medicina de células y tejidos. En este estudio, la longitud de las neuritas, la morfología nuclear y la toxicidad celular se evalúan a intensidades variables de ultrasonido de 92 kHz proporcionado por un elemento de disco piezocerámico e incidente sobre las neuronas SH-SY5Y in vitro. Los resultados sugieren que la estimulación aumenta la longitud de las neuritas hasta 2,73 veces probada a α = 0,05 de una manera dependiente de la intensidad. Además, la estimulación provoca una disminución estadísticamente significativa (α = 0,05) en el área nuclear y núcleos menos alargados, en 1,78 veces y 1,38 veces, respectivamente y también de una manera dependiente de la intensidad. Para intensidades máximas de la superficie del transductor que oscilan entre 0 y 39,11 W / cm2, se evaluó la toxicidad del ultrasonido de 92 kHz y se determinó un rango no tóxico mediante tinción con Caspasa-3 y Anexina V, además de imágenes de calcio mediante tinción con Calceína-AM. Se encontró que las intensidades de hasta 1.6 W / cm2 no son tóxicas para las células bajo los parámetros usados en este estudio.