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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.

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/cm

Highlights • DKI could detect early radiation-induced microstructural abnormalities after CCRT. • The ADC, Dmean, and FA of temporal lobe showed a unique time-dependent trajectory. • Kmean might be more sensitive to detection of effects in the late delayed phases. • White and grey matter all underwent microstructural changes after radiotherapy., 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

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

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.

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, PTEN 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 was performed and correlation between PTEN expression with the PFS and prognosis status using Cox regression for survival analysis was 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, should be considered as novel image markers that are correlated with PTEN expression and may be used to predict PTEN expression noninvasively. Combined radiological and clinical features can improve the performance of the classification of PTEN expression.

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). 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. 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. 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.

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.

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 $$(\ge 0.05\frac{W}{c{m}^{2}})$$ ( ≥ 0.05 W c m 2 ) 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 $$1.2\frac{W}{c{m}^{2}}\cdot $$ 1.2 W c m 2 ⋅ 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.

A novel neural stimulation system is demonstrated that is capable of delivering tunable ultrasonic stimulus at the cellular level and additionally providing feedback information towards dosage regulation. GHz aluminum nitride ultrasound transducers provide continuous wave stimulation to in vitro, retinoic acid differentiated SH-SY5Y neuroblastoma cells at 1.05 GHz. Results show stimulation of optically recorded calcium ion transients in SH-SY5Y cells, with during stimulation increases in FIFo of 1.5 ± 0.328, differing from pre-stimulation with p $a$ = 0.01.

Summary 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.

The directionality of collagen fibers across the anterior cruciate ligament (ACL) as well as the insertion of this key ligament into bone are important for understanding the mechanical integrity and functionality of this complex tissue. Quantitative analysis of three-dimensional fiber directionality is of particular interest due to the physiological, mechanical, and biological heterogeneity inherent across the ACL-to-bone junction, the behavior of the ligament under mechanical stress, and the usefulness of this information in designing tissue engineered grafts. We have developed an algorithm to characterize Optical Coherence Tomography (OCT) image volumes of the ACL. We present an automated algorithm for measuring ligamentous fiber angles, and extracting attenuation and backscattering coefficients of ligament, interface, and bone regions within mature and immature bovine ACL insertion samples. Future directions include translating this algorithm for real time processing to allow three-dimensional volumetric analysis within dynamically moving samples.